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[(key)-287.2(intr)-9.4(acellular)-296.1(signalli)-11.5(ng)-286.1(steps)-287.8(invol)-8.6(ved)-287.2(in)-288.4(the)-289.6(contr)-8.2(ac-)]TJ 0 -1.0527 TD [(tile)-340.7(respon)-7.8(se)-338.9(are)-340.4(shown)-339(in)-339.7(figure)-340.6(1)-336.5(using)-343.1(histami)-11.5(ne)-337.7(as)-338.9(a)]TJ 25.1977 33.9441 TD [(paradi)-9.4(gm.)-346.5(Hi)-7.8(stamine)-351(binds)-348.8(to)-345.3(the)-346.5(hist)-9(amine)-351.6(H)]TJ 7.472 0 0 6.641 497.083 770.003 Tm (1)Tj 9.963 0 0 9.963 504.227 771.647 Tm [(recept)-9.8(or)]TJ -19.5641 -1.0471 TD [(presen)-8.2(t)-338.9(o)0(n)-337.3(the)-340.8(cell)-338.7(surfa)-8.6(ce:)-335.5(this)-344.7(receptor)-342.9(is)-340.8(a)-336.9(member)-343.3(of)]TJ 0 -1.0528 TD [(the)-289.6(seven)-290.3(trans)-9.4(membrane)-294(domai)-9.7(n)-285.3(G)-283.5(prote)-8.2(in-coup)-9.7(led)-283.9(rec-)]TJ 0 -1.0471 TD [(eptor)-361(superf)-9.4(amily)-359.2(which)-357.7(is)-357.9(respon)-7.8(sible)-357.3(for)-358.3(the)-357.9(action)-357.3(of)]TJ 0 -1.0528 TD [(most)-385.3(imp)-7.8(ortant)-386.9(agonis)-8.6(ts)-380.7(in)-379.5(airway)-388.9(smoo)-7.4(th)-379.5(musc)-7.8(le)-379.9([10].)]TJ 0 -1.0471 TD [(Bin)-9.4(ding)-301.3(of)-304.7(hist)-9(amine)-306.1(to)-305.5(the)-306.7(H)]TJ 7.472 0 0 6.641 429.959 717.675 Tm (1)Tj 9.963 0 0 9.963 436.705 719.376 Tm [(receptor)-308.8(resul)-9.4(ts)-301(in)-305.5(stimu-)]TJ -12.7867 -1.0528 TD [(latio)-11.4(n)-319.4(o)0(f)-321.8(the)-329.4(associated)-329.4(G)-323.4(prote)-8.2(in,)-323(G)]TJ 7.97 0 0 7.97 456.661 708.888 Tm (q)Tj 9.963 0 0 9.963 460.63 708.888 Tm [(,)-319.1(whi)-8.6(ch)-320.6(diss)-7.8(ociates)]TJ -15.1881 -1.0471 TD [(relea)-9(sing)-331(the)-335.1(active)]TJ /F7 1 Tf 8.1261 0 TD (a)Tj /F8 1 Tf 0.9674 0 TD [(subuni)-8.1(t)-327.5(which)-334.9(is)-335.1(able)-330.6(to)-334(stimulate)]TJ -9.0935 -1.0527 TD [(pho)-8(spholipas)-8.7(e)-280(C)0(.)-284.7(This)-283.9(enzym)-7.8(e)-285.7(stimulates)-290.9(the)-283.9(breakdo)-7.7(wn)]TJ T* [(of)-338.9(the)-335.1(mem)-9(brane)-336.3(phospho)-6.5(lipid)-341(phospha)-6.9(tidyl)-341(inositol)-341.2(4,5)]TJ 0 -1.0471 TD [(bisph)-7.4(osphat)-8.5(e)-445(\(PIP)]TJ 7.472 0 0 6.641 383.017 665.405 Tm (2)Tj 9.963 0 0 9.963 386.759 667.049 Tm [(\),)-446.6(resultin)-10.7(g)-444.6(i)0(n)-442.1(the)-448.9(product)-9.7(ion)-442.8(of)-447(the)]TJ -7.7733 -1.0528 TD [(tw)-7.8(o)-507.2(intracell)-13.5(ular)-508.2(second)-513(mess)-9(engers)-514.6(inositol)-517.6(1,4,5)-509.5(tri-)]TJ 0 -1.0471 TD [(pho)-8(sphate)-447.1(\(IP)]TJ 7.472 0 0 6.641 365.953 644.485 Tm (3)Tj 9.963 0 0 9.963 374.06 646.129 Tm [(and)-446.6(diacylglyc)-10.3(erol)-445.6(\(DAG)-10.7(\).)-440.9(IP)]TJ 7.472 0 0 6.641 497.253 644.485 Tm (3)Tj 9.963 0 0 9.963 505.417 646.129 Tm [(dif)10.8(fuses)]TJ -19.6836 -1.0527 TD [(throu)-7.8(gh)-405.6(the)-409.1(cytos)-7.8(ol)-402.2(and)-406.7(b)-6.5(inds)-405(to)-407.9(speci)-8.2(fic)-405(sites)-409.7(\(the)-411.5(IP)]TJ 7.472 0 0 6.641 532.743 633.997 Tm (3)Tj 9.963 0 0 9.963 309.316 625.209 Tm [(recept)-9.8(or\))-358.3(on)-354.3(intracell)-13.5(ular)-354.6(calci)-9.8(um)-351.8(stor)-8.2(es,)-356.3(resultin)-10.7(g)-353.6(i)0(n)-351(re-)]TJ T* [(lease)-219.2(of)-213.7(calcium)-219.3(from)-214.3(the)-209.9(intr)-9.4(acellular)-222.1(stores)-216.2(into)-212.7(the)-209.9(cy)-7.6(to-)]TJ 0 -1.0471 TD [(plasm)-10.9(.)-313.4(This)-323.7(produce)-7.7(s)-314.9(a)-319.8(brief)-322.8(rise)-321.6(in)-316.9(the)-318.1(intr)-9.4(acellular)-324.5(free)]TJ 0 -1.0528 TD [(calci)-9.8(um)-385.9(conc)-9.6(entration)-10.7(.)-381.7(DAG)-8.4(,)-387.3(the)-386.3(other)-395.2(product)-391(of)-390.1(PIP)]TJ 7.472 0 0 6.641 532.743 592.157 Tm (2)Tj 9.963 0 0 9.963 309.316 583.37 Tm [(hyd)-8(rolysis,)-316.1(is)-312.4(able)-313.5(to)-316.9(activate)-316.5(prote)-8.2(in)-311.2(kinas)-7.8(e)-314.2(C)0(,)-307.5(whi)-8.6(ch)-309.2(in)]TJ T* [(turn)-257.4(can)-259.2(phospho)-6.5(rylate)-262.1(key)-253.1(targets,)-253.1(resultin)-10.7(g)-251.2(i)0(n)-254.3(a)0(n)-258(altered)]TJ 0 -1.0471 TD [(sensi)-9(tivity)-219(of)-219.4(the)-215.6(contr)-8.2(actile)-223.5(apparatus)-223.8(to)-214.5(calci)-9.8(um.)-215.6(Recen)-9.8(t-)]TJ 0 -1.0528 TD [(ly)58.7(,)-284.9(i)0(t)-290.8(has)-288.4(also)-291.6(been)-288.4(sugges)-7.4(ted)-289.6(that)-287.1(DAG)-292.9(may)-290.4(have)-288.4(an)-286.5(ad-)]TJ 0 -1.0471 TD [(ditio)-11(nal)-602.6(role)-610.6(as)-606.3(an)-605.1(agonist)-609.2(for)-608.7(nonvoltage-)-9.9(dependen)-7.3(t)]TJ 0 -1.0527 TD [(calci)-9.8(um)-334.7(channel)-8.9(s)-332(presen)-8.2(t)-333.2(i)0(n)-339.7(the)-335.1(tissue.)]TJ 1.0015 -1.0471 TD [(A)-226.6(n)0(u)21.2(m)0(b)12.4(e)0(r)-208.4(o)0(f)-213.7(o)0(t)18.9(h)0(e)15.1(r)-224.3(co)20.8(nt)18.9(ra)13.5(ct)18.5(il)16.5(e)-223.1(a)0(g)20.8(o)0(n)15.5(i)0(s)17.7(t)0(s)-210(c)0(o)15.1(u)0(p)21.2(l)0(e)12.8(d)-217(to)-214.5(re)19.2(ce)14.7(p-)]TJ -1.0015 -1.0528 TD [(to)13.2(rs)-334.4(ex)15.1(pr)19.6(es)13.9(se)19.6(d)-347.9(o)0(n)-337.3(a)0(i)18.4(r)0(w)15.7(a)0(y)-337.7(s)0(m)16.9(o)0(o)15.5(t)0(h)-334(m)0(u)12.4(s)0(c)19.6(l)0(e)-340.1(a)0(r)19.2(e)-348.3(al)18.4(so)-338.5(ab)20.8(le)-340.1(to)]TJ 0 -1.0471 TD [(st)17.7(im)15.7(ul)13.2(at)18.4(e)-331.2(c)0(o)20.8(n)0(t)13.2(r)0(a)19.2(c)0(t)18.5(i)0(l)16.5(e)-331.2(re)19.2(sp)14.4(on)21.2(se)14(s)-326.3(t)0(h)13.2(r)0(o)19.6(u)0(g)15.5(h)-330.8(th)18.9(e)-331.2(s)0(a)19.6(m)0(e)-323.7(i)0(n)18.9(t)0(r)17.3(a)0(c)14.7(e)0(l)18.4(-)]TJ 0 -1.0527 TD [(lu)13.2(la)18.4(r)-281.2(s)0(i)17.7(g)0(n)21.2(a)0(l)18.4(l)0(i)16.5(n)0(g)-274.7(p)0(a)20.8(t)0(h)18.8(w)0(a)16.9(y)67.5(.)-279.2(T)12.2(he)15.1(se)-270.6(ag)20.8(on)15.5(is)17.7(ts)17.7(,)-279.2(a)0(n)20.8(d)0(,)-274.3(w)12.4(he)15.1(re)-271(ch)15.1(ar)30.6(-)]TJ 0 -1.0471 TD [(ac)14.7(te)18.4(ri)17.3(ze)14.7(d,)-410.9(th)13.2(e)-422.3(r)0(e)19.2(c)0(e)14.7(p)0(t)18.9(o)0(r)13.9(s)-423.1(th)18.8(ro)19.6(ug)15.5(h)-421.9(w)0(h)17.3(i)0(c)12.8(h)-421.9(th)18.9(ey)-417.3(op)21.2(er)13.5(at)18.4(e,)-417(ar)19.2(e)]TJ 0 -1.0528 TD [(sh)14.4(ow)17.3(n)-325.1(i)0(n)-311.2(t)0(a)12.8(b)0(l)18.9(e)-325.5(1.)]TJ /F6 1 Tf 1.4795 -3.4485 TD [(Cont)-7.8(rol)-323.7(of)-333.2(intrac)-8.6(ellul)-10.6(ar)-320.6(calci)-9.4(um)-333.2(con)-7.6(centration)]TJ /F8 1 Tf -0.478 -2.0998 TD [(If)-317.7(th)18.9(e)-319.8(i)0(n)18.8(t)0(r)17.3(a)0(c)14.7(e)0(l)18.4(l)0(u)18.8(l)0(a)18.4(r)-321(ca)14.7(lc)18.4(iu)18.9(m)-322.6(r)0(e)13.5(s)0(p)20(o)0(n)15.5(s)0(e)-310.4(t)0(o)-311.2(a)0(n)-309.2(a)0(g)15.1(o)0(n)15.5(i)13.9(st)-312.4(su)14.3(ch)]TJ -1.0015 -1.0528 TD [(as)-259.2(hi)18.9(st)12(am)17.7(in)18.9(e)-268.6(i)0(s)-255.5(f)0(o)13.9(l)0(l)22.2(o)0(w)11.6(e)0(d)-258(i)0(n)-254.3(f)0(r)18(e)0(s)13.9(h)0(l)18.9(y)-268.2(is)17.7(ol)18.9(at)18.5(ed)-258(ai)12.8(rw)21.4(ay)-258(sm)11.2(oo)21.2(th)]TJ 0 -1.0471 TD [(mu)12.4(sc)19.6(le)18.4(,)-341.8(c)0(u)15.1(l)0(t)16.5(u)0(r)19.6(e)0(d)-332(a)0(i)18.5(r)0(w)15.7(a)0(y)-332(s)0(m)16.9(o)0(o)15.5(t)0(h)-334(m)0(u)18.1(s)0(c)19.6(l)0(e)-334.4(o)0(r)-333.2(p)0(e)15.1(r)0(m)16.5(e)0(a)20.4(b)0(i)13.2(l)0(i)22.2(z)0(e)14.7(d)]TJ 0 -1.0527 TD [(st)17.7(ri)17.3(ps)-475(of)-469.7(tr)17.3(ac)14.7(he)20.8(al)-470.9(mu)18.1(sc)13.9(le)18.4(,)-478.4(a)-479.2(ch)15.1(ar)19.2(ac)14.7(te)18.5(ri)17.3(st)17.7(ic)-470.9(pr)19.6(of)14(il)16.5(e)-479.2(o)0(f)-469.7(i)0(n)18.8(-)]TJ 0 -1.0471 TD [(tr)17.3(ac)14.7(el)18.5(lu)18.8(la)12.8(r)-332.4(c)0(a)20.4(l)0(c)18.4(i)0(u)13.2(m)-334(le)18.4(ve)20.8(ls)-323.8(fo)13.9(ll)16.5(ow)17.3(in)18.9(g)-330.8(a)0(g)15.1(o)0(n)21.2(i)0(s)17.7(t)-333.2(st)17.7(im)15.7(ul)13.2(at)18.4(io)18.9(n)-330.8(i)0(s)]TJ 0 -1.0528 TD [(ob)15.5(se)19.6(rv)13.9(ed)-280.8(\(f)18(ig)18.8(.)-284.9(2)0(\))-293.3([20].)-302.5(Experim)-11.3(ents)-302.9(designed)-306.4(to)-299.8(study)-297.6(in-)]TJ T* [(trace)-9(llular)-258.4(calcium)-259.2(signalling)-257.7(have)-254.2(utilized)-255.4(a)-251.6(range)-256.6(of)-247.8(ca)-8(l-)]TJ 0 -1.0471 TD [(cium)-9(-sens)-8.2(itive)-381.2(fluorescent)-388.6(probes)-383.3(whic)-9.8(h)-376.3(can)-378.7(be)-377.5(trapp)-8.2(ed)]TJ 0 -1.0527 TD [(insi)-9(de)-286.5(the)-283.9(cell)-287.5(such)-289.2(as)-287.7(Fura)-288.8(2)-279.6(and)-287.2(Fluo)-289.2(3.)-285.7(Combi)-8.4(ning)-284.3(the)]TJ 0 -1.0471 TD [(use)-271.3(of)-264.9(cells)-266.7("loade)-10.7(d")-260.6(wi)-7.8(th)-260(these)-270(agents)-270.7(with)-267.8(sophi)-7.4(sticated)]TJ 0 -1.0528 TD [(ima)-8.2(ging)-489.1(methods)-496.2(allows)-492.9(changes)-491.4(in)-487.6(calci)-9.8(um)-488.4(levels)-489.4(in)]TJ 0 -1.0471 TD [(singl)-9.8(e)-308.5(living)-319(cells)-317.9(to)-311.2(be)-314.9(follow)-9.2(ed)-309.2(in)-316.9("real)-313.1(time")-322.4([18,)-311.6(21].)]TJ 0 -1.0528 TD [(Fo)-6.4(llowing)-437.5(stimul)-10.4(ation)-435.8(of)-435.6(a)-433.7(cell)-435.4(with)-438.5(agonist,)-438.9(an)-434.4(initial)]TJ 0 -1.0471 TD [(rapid)-287(rise)-287.5(in)-282.7(intr)-9.4(acellular)-290.4(calci)-9.8(um)-283.5(levels)-290.2(occurs.)-287.4(This)-283.9(rea-)]TJ 0 -1.0527 TD [(che)-8.8(s)-212.5(a)-217.4(maxi)-9(mum)-219.1(within)-220.5(10\26115)-220.1(s)-218.2(and)-218.9(then)-216.4(rapid)-8.2(ly)-220.2(declines)]TJ /F13 1 Tf 10 0 0 10 122.607 258.758 Tm 0 0 0 1 k /GS3 gs (Ca)Tj 8 0 0 8 133.087 261.025 Tm (2+)Tj 10 0 0 10 153.607 268.758 Tm (IP)Tj 8 0 0 8 161.357 266.49 Tm (3)Tj 10 0 0 10 165.005 268.758 Tm (R)Tj 4.8303 1.1 TD (Ca)Tj 8 0 0 8 223.787 282.025 Tm (2+)Tj 10 0 0 10 78.857 298.508 Tm (Cytosol)Tj /F14 1 Tf 4.95 7.275 TD (b)Tj 0.125 -0.8399 TD (g)Tj 0.675 0.6649 TD (a)Tj /F13 1 Tf 1.55 0.525 TD (PLC)Tj 2.45 0.15 TD (PIP)Tj 8 0 0 8 189.577 373.989 Tm (2)Tj 10 0 0 10 153.607 334.257 Tm (IP)Tj 8 0 0 8 161.357 331.99 Tm (3)Tj 10 0 0 10 196.341 351.34 Tm -0.04 Tc [(DA)-10(G)]TJ 2.8731 5.0617 TD 0 Tc (Ca)Tj 8 0 0 8 235.552 404.224 Tm (2+)Tj 10 0 0 10 82.857 409.007 Tm (Agonist)Tj ET 0 0 0 1 K 0 J 0 j 0.5 w 3.864 M []0 d /GS4 gs 1 i 60.357 312.257 m 56.107 343.007 92.107 373.257 v 73.107 312.007 m 69.857 332.257 98.107 357.257 v 119.357 389.507 m 177.357 412.257 222.356 389.507 v 220.357 371.007 m 213.357 376.257 196.607 379.007 v 283.606 309.758 m 283.106 364.757 228.107 387.007 v 270.856 309.758 m 268.106 353.757 224.606 369.257 v 172.888 379.141 m 172.888 385.98 177.974 391.525 184.247 391.525 c 190.521 391.525 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2.9818 0 TD (,)Tj /F4 1 Tf 0.5065 0 TD (-3)Tj /F8 1 Tf 0.8251 0 TD (,)Tj /F4 1 Tf 0.5008 0 TD (-4)Tj /F8 1 Tf 1.0812 0 TD (and)Tj /F4 1 Tf 1.6958 0 TD (-6)Tj /F8 1 Tf -21.9769 -1.0641 TD [(are)-243.7(potential)-244.8(ca)-8(lcium)-239.7(e)-6.9(ntry)-240.3(pathways)-247.7(which)-243.8(are)-243.7(expres)-8.2(sed)]TJ 0 -1.0584 TD [(in)-225.8(cultured)-229.5(human)-229.3(airway)-235.2(smooth)-227.5(musc)-7.8(le)-226.2([23].)-222.9(The)-228.7(recent)]TJ 0 -1.0641 TD [(observ)-7.8(ation)-310.6(that)]TJ /F4 1 Tf 6.7262 0 TD [(HTRP)-8.7(3)]TJ /F8 1 Tf 3.2948 0 TD [(can)-310.4(be)-303.5(sti)-8.2(mulated)-315.7(by)-303.1(DA)-9.4(G)-306.3(pro-)]TJ -10.0211 -1.0584 TD [(vides)-229.7(an)-229.6(attractive)-236.6(mecha)-8.2(nism)-226(for)-233.1(sustained)-231.1(calci)-9.8(um)-226.6(entry)]TJ 0 -1.0641 TD [(in)-328.3(nonexci)-8.5(table)-333.7(cells,)-329.6(alth)-8.2(ough)-327.4(whether)-338.4(this)-327.7(is)-329.5(importan)-10.3(t)]TJ 0 -1.0584 TD [(in)-294.1(airw)-11.4(ay)-292.2(smoo)-7.4(th)-294.1(musc)-7.8(le)-300.2(remains)-299(to)-299.8(be)-297.8(determin)-10.7(ed,)-298.2(and,)]TJ 25.1977 66.1583 TD [(indeed)-7.8(,)]TJ /F4 1 Tf 3.2493 0 TD (HTRP4)Tj /F8 1 Tf 3.329 0 TD [(exhibits)-350.6(charact)-10.9(eristics)-353.8(more)-349.6(akin)-347.3(to)-345.3(the)]TJ -6.5783 -1.0471 TD [(elect)-9.8(rophys)-7.4(iological)-279(featu)-8.6(res)-272.9(of)-276.3(the)-272.5(putative)-281.5(airway)-275.1(myo-)]TJ 0 -1.0528 TD [(cyte)-342(channel)-8.9(.)]TJ /F6 1 Tf 2.5778 -2.6518 TD [(Relaxati)-11.1(on)-336.5(through)-329.3(G)]TJ 7.97 0 0 7.97 428.995 724.308 Tm (s)Tj 9.963 0 0 9.963 432.057 724.308 Tm [(-coupled)-338.6(receptors)]TJ /F8 1 Tf -11.3185 -1.747 TD [(Ai)14.9(rw)15.7(ay)-269.4(sm)16.9(oo)21.2(th)-271.4(mu)18.1(sc)19.6(le)-271.8(ce)20.4(ll)16.5(s)-275.1(e)0(x)15.1(p)0(r)19.6(e)0(s)13.9(s)-275.1(at)-266.1(le)18.4(as)13.9(t)-276.3(t)0(w)14.9(o)-273.9(re)19.2(ce)14.7(p-)]TJ -1.0015 -1.0527 TD [(to)13.2(rs)-186.4(co)15.1(up)15.5(l)13.9(e)0(d)-195.4(t)13.9(o)-199.9(a)0(d)15.1(e)0(n)20.8(y)0(l)13.2(y)0(l)-186(c)0(y)15.1(c)0(l)18.5(a)0(s)13.9(e)]TJ /F4 1 Tf 12.5021 0 TD [(vi)12.8(a)]TJ /F8 1 Tf 1.3885 0 TD 0.1993 Tc [(as)199.3(t)217(i)199.3(m)215(u)199.3(l)218.2(a)199.3(t)212.1(o)199.3(r)218.9(y)-0.6(Gp)199.3(r)213.3(o)199.3(t)218.1(e)199.3(i)217.7(n)]TJ -13.8906 -1.0471 TD 0 Tc (\(G)Tj 7.97 0 0 7.97 319.521 685.984 Tm (s)Tj 9.963 0 0 9.963 322.526 685.984 Tm [(\),)-338.5(na)20.8(me)12(ly)-334(th)13.2(e)]TJ /F7 1 Tf 5.6621 0 TD (b)Tj /F8 1 Tf 7.472 0 0 6.641 384.378 684.34 Tm (2)Tj 9.963 0 0 9.963 388.006 685.984 Tm [(-a)19.2(dr)14(en)20.8(oc)15.1(ep)15.1(t)13.9(o)0(r)-338.9([)0(4)14(,)-347.5(24)21.2(,)-347.5(2)0(5)15.5(])-343.8(an)15.1(d)-347.9(a)-342.6(pr)13.9(os)20(-)]TJ -7.8985 -1.0527 TD [(ta)12.8(no)21.2(id)-351(re)13.5(ce)20.4(pt)13.2(or)-350.2(\(p)19.6(ro)13.9(ba)20.8(bl)13.2(y)-359.3(E)0(P)]TJ 7.472 0 0 6.641 424.913 673.852 Tm (2)Tj 9.963 0 0 9.963 428.542 675.496 Tm [(\))-360.9([)0(4)14(,)-370.3(26]:)-376.9(there)-372.8(may)-375.7(be,)-372.2(in)]TJ -11.9672 -1.0471 TD [(add)-8.4(ition,)-295.9(a)-297.1(smal)-10.2(l)-293.4(popula)-7.4(tion)-298(of)-299(vasoactive)-305.4(intesti)-10.8(nal)-295.3(pep-)]TJ 0 -1.0527 TD [(tide)-378.1(recept)-9.8(ors,)-375.3(at)-379.9(least)-374.8(in)-379.5(some)-377.7(species)-381.2([27,)-374.1(28].)-379.8(Stimu-)]TJ 0 -1.0471 TD [(latio)-11.4(n)-490.2(o)0(f)-492.5(adenylyl)-495.4(cyclas)-9.4(e-coupl)-10.1(ed)-491.3(receptors)-498.5(resul)-9.4(ts)-488.8(in)]TJ 0 -1.0527 TD (G)Tj 7.97 0 0 7.97 316.516 633.656 Tm (s)Tj /F7 1 Tf 9.963 0 0 9.963 319.578 633.656 Tm (a)Tj /F8 1 Tf 0.8593 0 TD [(depend)-11.1(ent)-227(activati)-11.1(on)-223.5(of)-225.1(a)-6.9(denylyl)-232.4(cyclase)-232.5(in)-225.8(a)-223.1(manne)-7.8(r)]TJ -1.8893 -1.0471 TD [(ana)-8.8(logous)-480.5(to)-481.9(activati)-11.1(on)-479.5(of)-475.4(ph)-7.2(ospholipas)-9.5(e)-479.2(C)-477.8(pathways)-8.7(:)]TJ 0 -1.0527 TD [(thus,)-302.9(following)-304.1(binding)-300.3(of)-293.3(an)-297.8(agonist)-296.2(such)-300.6(as)-293.3(salbu)-7.8(tamol)]TJ 0 -1.0471 TD [(to)-396.6(the)]TJ /F7 1 Tf 2.7713 0 TD (b)Tj /F8 1 Tf 7.472 0 0 6.641 342.425 600.605 Tm (2)Tj 9.963 0 0 9.963 350.079 602.305 Tm [(adrenoc)-8.1(eptor)26(,)-393(G)]TJ 7.97 0 0 7.97 414.879 602.305 Tm (s)Tj 9.963 0 0 9.963 421.852 602.305 Tm [(diss)-7.8(ociates)-399.5(and)-395.3(the)-397.7(active)]TJ /F7 1 Tf 10.8689 0 TD (a)Tj /F8 1 Tf -22.1647 -1.0527 TD [(subuni)-8.1(t)-464.1(o)0(f)-464.1(G)]TJ 7.97 0 0 7.97 363.175 591.817 Tm (s)Tj 9.963 0 0 9.963 370.828 591.817 Tm [(stimul)-10.4(ates)-468.4(adenylyl)-466.9(cyclas)-9.4(e)-462.1(acti)-8.6(vity)-463.1(\(for)]TJ -6.1742 -1.0471 TD [(revie)-8.6(w)57.9(,)-358.9(see)-362.8([29]\).)-361.8(Aden)-7.4(ylyl)-360.6(cyclas)-9.4(e)-359.7(catal)-9.8(yses)-358.7(the)-363.6(break-)]TJ 0 -1.0528 TD [(down)-382.6(of)-373(adenosi)-9.7(ne)-377.5(triphosph)-8.7(ate)-375.4(\(A)101.1(TP\))-377.1(to)-379.5(cyclic)-380.4(adeno-)]TJ 0 -1.0471 TD [(sine)-394(monop)-7(hosphat)-9.3(e)-388.1(\(AMP\))-393.4(and)-389.7(cycli)-9.4(c)-388.1(AMP)-388.7(in)-390.9(turn)-388.3(is)]TJ 0 -1.0527 TD [(able)-370.4(to)-368.1(activate)-373.4(protein)-370.6(kinase)-367.5(A,)-369.3(which)-369(phospho)-6.5(rylates)]TJ 0 -1.0471 TD [(key)-349.8(intr)-9.4(acellular)-358.7(proteins)-355.5(and)-349.8(thus)-348.1(is)-352.2(responsibl)-11.1(e)-348.3(for)-346.9(the)]TJ 0 -1.0527 TD [(maj)-8.2(ority)-368.7(of)-361.6(the)-363.6(ph)-7.2(ysiologi)-8.7(cal)-364(respon)-7.8(se)-361.6(to)-362.4(sti)-8.2(mulati)-9.6(on)-360(of)]TJ /F7 1 Tf 0 -1.0471 TD (b)Tj /F8 1 Tf 7.472 0 0 6.641 314.872 516.926 Tm (2)Tj 9.963 0 0 9.963 318.614 518.627 Tm [(-adrenoce)-11.7(ptors)-230.9(\(fig)-8.6(.)-228(3\).)-236.8(Cyclic)-236.8(AM)-7.4(P)-227.6(i)0(s)-232.7(broken)-239.9(down)-234.6(by)]TJ -0.9333 -1.0528 TD [(intr)-9.4(acellular)-711.5(phospho)-6.5(diesteras)-11.1(es)-703.1(\(see)-706.6(below\).)-707.5(Ai)-7.8(rway)]TJ 0 -1.0471 TD [(smoo)-7.4(th)-328.3(musc)-7.8(le)-328.7(also)-331.4(contai)-10.1(ns)-327.1(a)-331.2(popula)-7.4(tion)-332.2(of)-327.5(musc)-7.8(arinic)]TJ 0 -1.0528 TD (M)Tj 7.472 0 0 6.641 318.161 485.575 Tm (2)Tj 9.963 0 0 9.963 325.927 487.219 Tm [(receptors)-407.5(whi)-8.6(ch)-400.3(are)-403(neg)-8.4(atively)-405.9(couple)-7.8(d)-399.1(t)0(o)-402.3(a)0(d)-7.6(enylyl)]TJ -1.6673 -1.0471 TD [(cyc)-8.8(lase)]TJ /F4 1 Tf 3.2436 0 TD (via)Tj /F8 1 Tf 1.5364 0 TD [(an)-326.3(inhi)-7.8(bitory)-335.3(G)-329.1(protein)-336.5(\(G)]TJ 7.97 0 0 7.97 463.861 476.787 Tm (i)Tj 9.963 0 0 9.963 466.016 476.787 Tm [(\))-326.7([30\26132])-8.5(.)-330.4(Stimu-)]TJ -15.7287 -1.0528 TD [(latio)-11.4(n)-330.8(o)0(f)-338.9(musc)-7.8(arinic)-341.8(M)]TJ 7.472 0 0 6.641 402.123 464.655 Tm (2)Tj 9.963 0 0 9.963 409.209 466.299 Tm [(receptors)-344.9(by)-337.3(acetylchol)-10.7(ine)-340.8(inhi-)]TJ -10.0267 -1.0471 TD [(bits)-424.4(activati)-11.1(on)-416.9(of)-418.5(adenyl)-7.8(yl)-419.3(cyclas)-9.4(e,)-417(which)-425.9(results)-424.2(in)-419.3(an)]TJ 0 -1.0528 TD [(acu)-8.8(te)-362.8(loweri)-9.6(ng)-360(of)-367.3(intracellula)-12.9(r)-366.6(cyclic)-369.1(AMP)-365.9(levels.)-370.2(Thus)]TJ 0 -1.0471 TD [(intr)-9.4(acellular)-415.6(cy)-7.6(clic)-412.6(AMP)-411.4(concent)-8.9(ration)-415.4(is)-409.1(contr)-8.2(olled)-413(by)]TJ 0 -1.0527 TD [(the)-261.2(counte)-7.8(rbalance)-262.1(between)-263.2(acti)-8.6(vation)-260.1(of)-253.5(G)]TJ 7.97 0 0 7.97 481.096 424.46 Tm (s)Tj 9.963 0 0 9.963 484.157 424.46 Tm [(-coupl)-9(ed)-252.3(rec-)]TJ -17.5497 -1.0528 TD [(eptor)-8.2(s)-314.9(and)-315.7(G)]TJ 7.97 0 0 7.97 361.247 413.972 Tm (i)Tj 9.963 0 0 9.963 363.401 413.972 Tm [(-coupled)-318.2(recept)-9.8(ors)-318.1(together)-320.6(with)-319(regul)-8.2(ation)]TJ -5.4288 -1.0471 TD [(at)-408.3(the)-409.1(level)-413.4(of)-407.2(breakdo)-7.7(wn)-409.5(of)-407.2(cycli)-9.4(c)-405.2(AMP)-411.4(by)-405.6(phospho)-6.5(-)]TJ 0 -1.0527 TD [(diest)-10.2(erase)-337.9(isoforms)-341.6(\(see)-342.4(below\).)]TJ ET 0 0 0 1 K 0 J 0 j 0.49 w 3.864 M []0 d /GS4 gs 1 i 310.637 260.542 m 312.352 306.357 342.731 328.407 v 323.377 260.542 m 326.562 296.312 348.611 310.522 v 370.661 346.782 m 511.536 397.251 535.056 263.972 v 426.276 337.962 m 514.476 336.982 522.806 257.602 v S BT /F13 1 Tf 9.8 0 0 9.8 401.286 197.823 Tm 0 0 0 1 k /GS3 gs (Relaxation)Tj ET /GS4 gs 397.074 209.957 45.325 -17.762 re S BT 9.8 0 0 9.8 332.687 368.832 Tm /GS3 gs (Agonist)Tj 0 -12.55 TD (Cytosol)Tj 6.05 5.6685 TD -0.12 Tc [(AT)-120(P)]TJ 3.35 0.1315 TD 0 Tc (cAMP)Tj -1.7875 -4.6 TD (R)Tj 1.0625 0.0192 TD (C)Tj 2.35 0.0125 TD (R)Tj 0.8924 0.0192 TD (C)Tj -4.0924 2.0241 TD (PKA)Tj 3.275 -0.1125 TD (PKA)Tj -3.575 5.425 TD -0.03 Tc (AC)Tj /F14 1 Tf -1.825 -0.5875 TD 0 Tc (a)Tj -0.9842 0.215 TD (b)Tj 0.2342 -0.9107 TD (g)Tj ET /GS4 gs 400.429 333.062 m 400.429 340.436 405.475 346.414 411.699 346.414 c 417.923 346.414 422.969 340.436 422.969 333.062 c 422.969 325.688 417.923 319.71 411.699 319.71 c 405.475 319.71 400.429 325.688 400.429 333.062 c h 396.497 317.689 m 391.306 312.676 383.528 312.308 379.125 316.867 c 374.721 321.427 375.36 329.187 380.551 334.201 c 385.742 339.214 393.52 339.582 397.924 335.022 c 402.327 330.463 401.689 322.702 396.497 317.689 c h 344.201 347.027 m 351.307 313.83 l 355.227 300.722 354.247 315.3 v 354.369 314.809 m 349.837 336.859 l 348.857 353.274 353.879 337.104 v 353.756 337.349 m 357.431 319.342 l 361.964 304.275 361.229 320.689 v 361.229 320.199 m 356.574 341.637 l 355.227 358.909 360.004 342.372 v 360.004 342.739 m 364.414 322.159 l 368.334 310.032 367.844 323.629 v 367.844 323.629 m 363.067 347.394 l 361.229 363.197 366.497 347.884 v 366.497 348.129 m 371.764 322.404 l 372.499 320.689 l 373.112 319.587 l 373.969 318.24 l 375.806 317.627 l 422.969 309.91 m 416.477 330.857 402.634 311.747 v S 422.885 310.183 m 424.525 310.684 l 424.139 306.083 l 421.245 309.681 l 422.885 310.183 l f* 422.356 290.555 m 432.646 306.97 442.814 287.37 v S 422.508 290.797 m 423.962 289.888 l 420.236 287.161 l 421.054 291.706 l 422.508 290.797 l f* 406.064 268.505 m 406.064 255.275 l 414.639 255.275 l 412.802 257.602 l 413.659 258.95 l 414.272 259.93 l 413.781 260.787 l 414.026 262.502 l 413.414 263.85 l 414.516 264.952 l 414.884 266.055 l 414.026 268.627 l 406.064 268.505 l h 416.844 268.382 m 424.561 268.382 l 424.561 255.397 l 416.966 255.397 l 416.721 256.5 l 415.986 257.602 l 415.864 258.092 l 416.354 258.827 l 416.844 259.807 l 416.721 260.542 l 416.354 261.277 l 416.721 262.012 l 416.721 262.992 l 416.109 263.85 l 416.844 264.707 l 417.212 265.442 l 417.456 266.545 l 416.966 267.402 l 416.844 268.382 l h 440.731 268.015 15.435 -13.107 re 447.959 254.785 m 447.959 255.765 l 447.102 256.99 l 447.346 258.092 l 448.449 259.317 l 447.959 260.297 l 447.959 261.032 l 448.449 262.012 l 447.469 263.482 l 448.081 264.34 l 448.816 265.075 l 448.816 266.422 l 448.204 267.892 l 427.746 223.18 m 422.111 238.002 424.194 250.13 v S 427.644 223.447 m 429.245 224.062 l 429.18 219.444 l 426.043 222.832 l 427.644 223.447 l f* 420.152 223.425 m 420.152 250.375 l S 420.152 223.711 m 421.866 223.711 l 420.152 219.424 l 418.436 223.711 l 420.152 223.711 l f* 412.924 223.67 m 419.539 243.882 417.334 250.13 v S 413.012 223.942 m 414.643 223.412 l 411.687 219.864 l 411.381 224.472 l 413.012 223.942 l f* 383.156 336.124 m 384.381 333.797 l 384.749 330.979 l 384.872 325.344 l 384.994 323.139 l 386.586 320.567 l 387.689 318.729 l 387.934 317.014 l 387.566 315.177 l 387.199 313.83 l 376.664 321.057 m 377.644 322.527 l 379.849 323.752 l 382.421 323.874 l 384.994 323.629 l 352.532 350.089 m 351.919 353.642 l 350.816 356.337 l 349.102 358.664 l 347.876 361.727 l S 352.482 350.371 m 354.171 350.669 l 353.226 346.148 l 350.793 350.073 l 352.482 350.371 l f* BT /F8 1 Tf 7.97 0 0 7.97 309.26 180.34 Tm 0 g /GS2 gs [(Fig.)-327.1(3.)-331.2(\261)-332.2(Pathways)-340.7(involved)-342.6(in)-346.7(airway)-339(smooth)-346.9(muscle)-337.8(relaxation.)-345(Fol-)]TJ 0 -1.0599 TD [(lowing)-343.2(binding)-338.6(of)-344.5(agonist)-345.9(to)-346.7(receptor)-338.5(\()]TJ /F4 1 Tf 15.8623 0 TD (e.g.)Tj /F8 1 Tf 1.7783 0 TD (the)Tj /F7 1 Tf 1.5507 0 TD (b)Tj /F8 1 Tf 5.977 0 0 5.313 466.639 170.589 Tm (2)Tj 7.97 0 0 7.97 472.365 171.893 Tm [(adrenoreceptor)10.3(\),)-345.6(the)]TJ -20.4645 -1.0599 TD [(associated)-394.6(stimulatory)-399.6(G)-398.8(protein)-401.8(\(Gs\))-401.1(dissociates)-397.1(freeing)-398.6(the)-400.5(stimula-)]TJ 0 -1.067 TD (tory)Tj /F7 1 Tf 1.8636 0 TD (a)Tj /F8 1 Tf 0.9105 0 TD [(subunit)-268.7(from)]TJ /F7 1 Tf 5.3846 0 TD (b)Tj /F9 1 Tf 0.8251 0 TD (c)Tj /F8 1 Tf 0.4979 0 TD 0.2764 Tc (.G)Tj 6.376 0 0 6.376 394.753 154.942 Tm 0 Tc (s)Tj /F7 1 Tf 0.3823 0 TD (a)Tj /F8 1 Tf 7.97 0 0 7.97 403.483 154.942 Tm [(is)-276.8(able)-269.4(to)-275.6(activate)-270.8(adrenylyl)-275.6(cyclase)-269.3(\(AC\),)]TJ -11.822 -1.0599 TD [(which)-505.5(catalyses)-503.4(the)-507.2(breakdown)-501(of)-508.1(adenosine)-500.9(triphosphate)-500.5(\(A)108.2(TP\))-513.6(to)]TJ T* [(cyclic)-295(adenosine)-294.6(monopho)14.4(sphate)-294.8(\(cAMP\);)-292.2(this)-303.4(in)-297(turn)-292.9(activates)-298.4(protein)]TJ 0 -1.067 TD [(kinase)-287.7(A)-292.1(\(PKA\),)-283.2(leading)-286.8(to)-289.8(the)-286.7(dissociation)-283.4(of)-294.7(the)-286.7(catalytic)-285.3(subunit)-290(\(C\))]TJ 0 -1.0599 TD [(from)-340.8(the)-343.6(regulatory)-344.8(subunit)-339.8(\(R\).)-339.1(The)-343.9(catalytic)-342.2(subunit)-339.8(is)-347.9(able)-340.5(to)-346.7(phos-)]TJ T* [(phorylate)-325.4(key)-327(targets)-323.7(within)-324.3(the)-336.5(cell)-328.7(leading)-329.5(to)-325.4(relaxation.)]TJ ET /GS4 gs 92.241 768.871 m 92.241 640.212 l S 0.461 w 92.676 636.794 m 283.268 636.794 l 92.241 640.456 m 88.767 640.456 l 92.241 670.119 m 88.767 670.119 l 92.241 699.842 m 88.767 699.842 l 92.241 729.566 m 88.767 729.566 l 92.241 760.119 m 88.767 760.119 l 125.847 636.794 m 125.847 633.376 l 165.045 636.794 m 165.045 633.376 l 204.49 636.794 m 204.49 633.376 l 243.934 636.794 m 243.934 633.376 l S BT /F13 1 Tf 0 11.017 -9.8 0 68.244 683.21 Tm 0 0 0 1 k /GS3 gs (Ca)Tj 0 8.814 -7.84 0 66.022 694.756 Tm (2+)Tj 0 11.017 -9.8 0 68.244 702.997 Tm ( nM)Tj ET /GS4 gs 283.103 636.794 m 283.103 633.376 l S BT 9.8 0 0 9.8 68.098 757.604 Tm /GS3 gs (1000)Tj 0.4391 -3.1716 TD (750)Tj 0 -3.0601 TD (500)Tj 11.017 0 0 9.8 70.906 666.856 Tm (250)Tj 0.9028 -2.9866 TD (0)Tj 3.6188 -1.4966 TD [(10)-2631.2(20)]TJ 7.1606 0.0091 TD (30)Tj 3.6115 -0.0091 TD (40)Tj 3.4349 0.0283 TD -0.0109 Tc (50)Tj -8.4 -1.8384 TD 0 Tc (Time s)Tj ET /GS4 gs 126.508 756.054 m 126.508 764.477 l S 126.508 756.333 m 128.179 756.333 l 126.508 752.156 l 124.838 756.333 l 126.508 756.333 l f* BT 8.717 0 0 9.8 121.789 769.332 Tm /GS3 gs (HA)Tj ET /GS4 gs 250.438 754.711 m 250.438 762.89 l S 250.438 754.99 m 252.108 754.99 l 250.438 750.813 l 248.767 754.99 l 250.438 754.99 l f* BT 8.717 0 0 9.8 242.901 769.674 Tm /GS3 gs (Mep)Tj ET 0.49 w /GS4 gs 105.136 653.446 m 124.246 653.446 l 125.961 660.184 l 126.941 667.534 l 128.411 683.459 l 130.616 712.369 l 131.474 733.438 l 131.474 740.176 l 132.576 750.098 137.599 734.051 v 137.476 734.418 m 143.479 717.268 l 147.276 706.733 l 152.176 693.504 l 153.646 689.583 l 156.586 683.214 l 159.649 678.191 l 160.874 676.721 l 162.956 674.884 l 166.509 672.434 l 170.551 670.841 l 186.966 669.494 l 239.029 668.514 l 243.684 668.146 l 246.134 667.779 l 248.216 667.166 l 249.809 666.309 l 250.911 665.084 l 252.136 661.409 l 252.504 658.836 l 253.729 656.754 l 255.811 655.039 l 258.751 653.324 l 263.039 652.344 l 268.796 651.854 l S BT /F8 1 Tf 7.97 0 0 7.97 58.28 593.178 Tm 0 g /GS2 gs 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350.192 288.68 Tm (2)Tj 9.963 0 0 9.963 358.129 290.381 Tm [(recept)-9.8(ors)-426.2(inhibit)-9.2(s)-423.1(cyclic)-426(AM)-7.4(P)-421.1(form)-9.4(ation)-424.4(in)]TJ -4.8996 -1.0528 TD [(airw)-11.4(ay)-258(smoo)-7.4(th)-260(muscle.)-268.6(It)-261.6(can)-259.2(thus)-262.7(be)-263.7(seen)-261.1(that,)-264.7(in)-260(airway)]TJ 0 -1.0471 TD [(smoo)-7.4(th)-305.5(musc)-7.8(le,)-300.6(a)-302.8(seri)-8.6(es)-304.7(of)-304.7(complex)-307.6(co)-7.6(ntrolling)-308.2(mecha)-8.2(n-)]TJ 0 -1.0527 TD [(ism)-9(s)-468.6(have)-476.2(evolve)-7.8(d)-473.1(which)-477.2(have)-470.5(resul)-9.4(ted)-471.7(in)-476.2(cholinergic)]TJ 0 -1.0471 TD [(sti)-8.2(mulatio)-10.3(n)-256.8(resultin)-10.7(g)-256.8(i)0(n)-260(both)-255.8(con)-8.4(traction)-266(through)-265.4(stimula-)]TJ 0 -1.0528 TD [(tion)-480.1(o)-6.5(f)-474.7(phospho)-6.5(lipase)-483.7(C-dependen)-15.1(t)-475.5(pathways)-486.7(and)-475(also)]TJ T* 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[(ve)15.1(al)18.5(ed)-394.6(th)13.2(e)-405.2(e)0(x)20.8(i)0(s)17.7(t)0(e)12.8(n)0(c)20.8(e)-405.2(of)-401.5(at)-397(le)18.4(as)19.6(t)-407.2(s)0(e)13.9(v)0(e)20.8(n)-410.5(ph)21.2(os)20(ph)15.5(od)15.5(ie)18.4(st)17.7(er)19.2(as)13.9(e)]TJ 0 -1.0527 TD [(fa)19.2(mi)15.7(li)16.5(es)13.9(,)-495.5(e)0(a)14.7(c)0(h)-491.3(f)0(a)19.2(m)0(i)15.7(l)0(y)-493.3(c)0(o)20.8(n)0(t)13.2(a)0(i)18.5(n)0(i)18.9(n)0(g)-490.9(a)-501.9(nu)21.2(mb)12.4(er)-492.9(of)-486.8(va)15.1(ri)17.3(an)15.1(ts)17.7(,)]TJ T* [(so)20(me)-289.6(re)19.2(su)14.4(lt)16.5(i)13.9(n)0(g)-286.1(a)0(s)-287.7(a)-297.1(co)20.8(ns)14.4(eq)20.8(ue)15.1(nc)20.8(e)-297.1(o)0(f)-282(a)0(l)12.8(t)0(e)18.4(r)0(n)19.6(a)0(t)18.4(i)0(v)13.2(e)-291.4(sp)14.4(li)22.2(ci)12.8(ng)-286.1(of)]TJ 0 -1.0471 TD [(ge)15.1(ne)-269.4(fa)19.2(mi)15.7(ly)-265.7(me)12(mb)18.1(er)19.2(s)-280.8([)0(6)19.6(4].)-282.3(In)-287.7(airway)-292.1(smoo)-7.4(th)-288.4(musc)-7.8(le,)-289.2(the)]TJ 0 -1.0528 TD [(most)-322.7(imp)-7.8(ortan)-8.2(t)-316.1(phospho)-6.5(diest)-10.2(erase)-326.5(isoforms)-330.2(appear)-326.1(to)-322.6(be)]TJ 0 -1.0471 TD [(memb)-9.7(ers)-295.7(of)-293.3(the)-295.3(type)-301.7(III)-297.3(and)-292.9(type)-296.1(IV)-297.3(fami)-10.6(lies)-293.9([4,)-299.4(65\26167].)]TJ 0 -1.0527 TD [(Physio)-7.4(logical)-297.8(contr)-8.2(ol)-294.1(of)-293.3(cellu)-9.4(lar)-291.2(cycli)-9.4(c)-291.4(A)0(M)-7.4(P)-290.2(conten)-7.8(t)-293.4(\(by)]TJ 0 -1.0471 TD [(regul)-8.2(ating)-458.5(cycli)-9.4(c)-456.4(AMP)-456.9(b)-6.5(reakdown\))-464.3(appears)-464.6(to)-459.2(be)-457.2(pre-)]TJ 0 -1.0527 TD [(domin)-9.3(antly)-413(due)-412.4(to)-407.9(the)-414.8(type)-415.6(IV)-359.9(isoform)-419.3(with)-410.1(a)-410.9(varia)-8.6(ble)]TJ 0 -1.0471 TD [(contr)-8.2(ibution)-399.4(from)-402(type)-398.5(III)-394(phospho)-6.5(diest)-10.2(erase)-400.5(dependen)-7.3(t)]TJ 0 -1.0528 TD [(upon)-287.6(the)-289.6(species)-290.2(studied.)-290.9(The)-285.7(tw)-7.8(o)-285.3(families)-293.1(can)-287.6(be)-286.5(distin-)]TJ 0 -1.0471 TD [(guish)-7.4(ed)-314.9(by)-320.2(their)-323.6(regulatory)-323.7(cha)-8.8(racteristics)-14.5(:)-316.1(wherea)-11.3(s)-314.9(both)]TJ 0 -1.0527 TD [(the)-386.3(type)-387.1(III)-382.7(and)-389.7(type)-381.4(IV)-388.3(phospho)-6.5(diesteras)-11.1(e)-382.4(famili)-11.2(es)-384.4(are)]TJ 0 -1.0471 TD [(relativel)-13.5(y)-308.1(cyc)-8.8(lic)-314.7(AMP-sel)-10.3(ective,)-318.2(members)-322.5(of)-310.4(the)-318.1(type)-313.1(III)]TJ 0 -1.0528 TD [(phospho)-6.5(diesteras)-11.1(e)-325.5(fami)-10.6(ly)-322.6(are)-329.1(stimul)-10.4(ated)-330.6(by)-325.9(cyclic)-329.2(GM)-7.4(P)102.4(.)]TJ 0 -1.0471 TD [(As)-439.1(discu)-7.8(ssed)-444(above,)-443.2(relativel)-13.5(y)-433.3(lit)-9.4(tle)-439.9(attentio)-10.7(n)-438.9(has)-442.1(been)]TJ 0 -1.0527 TD [(paid)-284.7(to)-277.1(cyclic)-283.7(GM)-7.4(P)-278.8(a)0(s)-276.3(a)-280(mediator)-289.6(of)-276.3(relax)-8.6(ation)-282.1(in)-277.1(a)-6.9(irway)]TJ 0 -1.0471 TD [(smoo)-7.4(th)-220.2(muscle)-228.3(\(as)-221.7(opposed)-223.2(to)-220.2(vascul)-9(ar)-219.8(smoo)-7.4(th)-220.2(musc)-7.8(le,)-220.9(in)]TJ 0 -1.0528 TD [(which)-340.6(cyclic)-340.6(GMP)-337.4(has)-333.9(a)-336.9(clear-cut)-335.1(role\).)]TJ /F6 1 Tf 3.1184 -3.1013 TD [(Ion)-338.4(chan)-7.6(nels)-336.3(in)-333.2(airw)-9.8(ay)-331.6(smoot)-9(h)-335.7(muscle)]TJ /F8 1 Tf -2.1169 -2.0998 TD [(Ai)14.9(rw)15.7(ay)-263.7(sm)11.2(oo)21.2(th)-271.4(m)13.2(u)0(s)14.4(c)0(l)18.4(e)-280(ce)20.4(ll)16.5(s)-275.1(e)0(x)15.1(h)0(i)18.9(b)0(i)18.9(t)-276.3(ma)12(rk)19.6(ed)-269.4(st)17.7(ab)20.8(il)16.5(it)16.5(y)-279.6(o)0(f)]TJ -1.0015 -1.0528 TD 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[(In)-299(so)20(me)-301(sp)20(ec)14.7(ie)18.4(s)-303.6(\()0(i)17.3(n)0(c)15.1(l)0(u)18.9(d)0(i)18.9(n)0(g)-297.4(h)0(u)15.5(m)0(a)17.7(n)0(\))13.9(,)-302(sl)17.7(ow)-301.4(w)12.4(a)0(v)15.1(e)-308.5(ac)20.4(ti)16.5(vi)18.9(ty)-299.8(is)]TJ 0 -1.0471 TD [(ob)15.5(se)19.6(rv)19.6(ed)15.1(.)]TJ /F6 1 Tf 7.5969 -3.107 TD [(Calcium)-346.1(channels)]TJ /F8 1 Tf -6.5953 -2.0998 TD [(Th)17.1(er)19.2(e)-308.5(a)0(r)19.2(e)-302.8(a)-302.8(n)0(u)15.5(m)0(b)18.1(e)0(r)-299.4(o)0(f)-282(f)0(o)19.6(r)0(m)16.5(s)-309.2(of)-293.3(vo)21.2(lt)16.5(ag)15.1(e-)19.2(de)15.1(pe)20.8(nd)15.5(en)20.8(t)-304.7(c)0(a)14.7(l)0(-)]TJ -1.0015 -1.0471 TD [(ci)18.4(um)-317.7(ch)20.8(an)15.1(ne)20.8(l)-321.8(w)0(h)17.3(i)0(c)12.8(h)-319.4(di)18.9(f)20.4(f)0(e)13.5(r)-321(in)-311.2(th)13.2(ei)18.4(r)-321(s)0(e)19.6(l)0(e)12.8(c)0(t)18.4(i)0(v)18.9(i)0(t)16.5(y)-319.4(fo)13.9(r)-321(d)0(i)18.9(v)0(a)15.1(l)13.9(en)15.1(t)]TJ 0 -1.0528 TD 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[(ch)15.1(an)20.8(ne)15.1(ls)-255.5(ar)19.2(e)-268.6(f)0(o)19.6(r)0(m)16.5(e)0(d)-258(b)0(y)-257.6(h)0(e)20.8(t)0(e)18.4(r)0(o)13.9(-)0(o)19.6(l)0(i)16.5(g)0(o)21.2(m)0(e)12(r)0(i)17.3(c)-262.9(co)15.1(mp)18.1(le)18.4(xe)15.1(s)-263.7(c)0(o)15.1(n)0(-)]TJ 0 -1.0527 TD [(si)17.7(st)17.7(in)18.9(g)-507.2(o)0(f)-498.2(a)0(n)]TJ /F7 1 Tf 5.793 0 TD (a)Tj /F8 1 Tf 7.472 0 0 6.641 122.23 300.189 Tm (1)Tj 9.963 0 0 9.963 131.017 301.833 Tm [(su)20(bu)15.5(ni)18.9(t)-509.6(w)0(h)17.3(i)0(c)18.4(h)-507.2(fo)19.6(rm)16.5(s)-508.4(t)0(h)13.2(e)-507.6(po)21.2(re)-498.6(of)-498.2(th)13.2(e)]TJ -7.301 -1.0471 TD [(ch)15.1(an)20.8(ne)15.1(l)-208(a)0(n)20.8(d)-205.6(pr)13.9(ov)21.2(id)18.9(es)-202.3(th)18.9(e)-206(e)0(x)15.1(t)0(r)17.3(a)0(c)20.4(e)0(l)18.4(l)0(u)13.2(l)0(a)18.4(r)-207.2(bi)18.9(nd)15.5(in)18.9(g)-205.6(s)0(i)17.7(t)0(e)-197.8(f)0(o)13.9(r)-207.2(mo)18.1(st)]TJ 0 -1.0527 TD [(ag)15.1(on)21.2(is)17.7(ts)-301(an)15.1(d)-308.1(a)0(n)15.1(t)0(a)18.4(g)0(o)15.5(n)0(i)18.9(s)0(t)17.7(s)-309.2(to)18.9(ge)15.1(th)18.9(er)-305.1(w)12.4(i)0(t)16.5(h)-313.7(a)]TJ /F7 1 Tf 16.1782 0 TD (b)Tj /F8 1 Tf 0.5463 0 TD (,)Tj /F7 1 Tf 0.5577 0 TD (a)Tj /F8 1 Tf 7.472 0 0 6.641 236.693 279.269 Tm (2)Tj 9.963 0 0 9.963 240.321 280.913 Tm (-)Tj /F7 1 Tf 0.3187 0 TD (d)Tj /F8 1 Tf 0.7967 0 TD [(an)15.1(d)-308.1(p)0(o)15.5(s)0(-)]TJ -19.3877 -1.0471 TD [(si)17.7(bl)18.9(y)]TJ /F9 1 Tf 2.0884 0 TD (c)Tj /F8 1 Tf 0.6999 0 TD [(su)20(bu)15.5(ni)18.9(t.)-191.3(Al)14.9(t)13.9(h)0(o)15.5(u)0(g)15.5(h)-194.2(vo)15.5(lt)16.5(ag)20.8(e-)13.5(de)20.8(pe)15.1(nd)21.2(en)15.1(t)-196.6(c)0(a)14.7(l)0(c)18.4(i)0(u)18.9(m)-203.1(ch)15.1(an)20.8(-)]TJ -2.7884 -1.0527 TD [(ne)15.1(ls)-420.5(ca)14.7(n)-433.2(b)0(e)-423(r)0(e)13.5(a)0(d)20.8(i)0(l)16.5(y)-433.2(id)13.2(en)20.8(ti)16.5(fi)17.3(ed)-423(in)-425(fr)12.4(es)19.6(hl)18.9(y)-433.2(i)0(s)17.7(o)0(l)13.2(a)0(t)18.5(e)0(d)-423(a)0(i)18.5(r)0(w)15.7(a)0(y)]TJ 0 -1.0471 TD [(my)18.1(oc)15.1(yt)18.9(es)-287.7(an)15.1(d)-296.7(c)0(h)20.8(a)0(n)15.1(n)0(e)15.1(l)-293.4(ac)14.7(ti)16.5(vi)18.9(ty)-288.4(is)-289.6(in)18.9(cr)19.2(ea)14.7(se)19.6(d)-302.4(b)0(y)-286.1(c)0(h)20.8(o)0(l)13.2(i)0(n)18.9(e)0(r)30.6(g)0(i)13.2(c)]TJ 0 -1.0527 TD [(ag)15.1(en)20.8(ts)-392.1(su)20(ch)-394.6(as)-390.1(me)17.7(th)13.2(ac)20.4(ho)15.5(li)16.5(ne)20.8(,)-398.7(t)0(h)13.2(e)-399.5(ov)21.2(er)13.5(al)18.4(l)-401.5(c)0(o)20.8(n)0(t)13.2(r)0(i)17.3(b)0(u)21.2(t)0(i)16.5(o)0(n)-388.5(o)0(f)]TJ 0 -1.0471 TD [(th)18.9(es)13.9(e)-513.3(c)0(h)15.1(a)0(n)15.1(n)0(e)20.8(l)0(s)-511.6(t)0(o)-510.4(a)0(g)20.8(o)0(n)15.5(i)0(s)17.7(t)0(-)17.3(i)0(n)18.9(d)0(u)15.5(c)0(e)20.4(d)-518.6(co)15.1(nt)18.9(ra)19.2(ct)18.4(il)16.5(e)-519(r)0(e)19.2(s)0(p)14.4(o)0(n)21.2(s)0(e)13.9(s)]TJ 0 -1.0528 TD [(se)19.6(em)12(s)-371.8(s)0(m)16.9(a)0(l)18.4(l)0(.)-367.7(A)0(s)-365.2(m)0(e)17.7(n)0(t)13.2(i)13.9(on)15.5(ed)-366.1(ab)20.8(ov)15.5(e,)-365.7(th)18.9(e)-376.7(p)0(r)19.6(o)0(l)18.9(o)0(n)15.5(g)0(e)20.8(d)-376.3(ri)17.3(se)-367.3(in)]TJ 0 -1.0471 TD [(in)18.9(tr)17.3(ac)14.7(el)18.5(lu)18.8(la)18.4(r)-207.2(c)0(a)14.7(l)0(c)18.4(i)0(u)18.9(m)-208.8(le)18.4(ve)15.1(ls)-192.9(se)14(en)-195.4(fo)19.6(ll)16.5(ow)17.3(in)18.9(g)-205.6(s)0(t)17.7(i)0(m)15.7(u)0(l)13.2(a)0(t)18.4(i)0(o)18.9(n)-205.6(wi)14.9(th)]TJ 0 -1.0528 TD [(ag)15.1(on)21.2(is)17.7(ts)-352.2(su)20(ch)-349.1(as)-350.2(hi)18.9(st)17.7(am)12(i)13.9(n)0(e)-354.7(i)13.9(s)-360.5(i)0(n)18.9(s)0(e)13.9(n)0(s)20(i)0(t)16.5(i)0(v)18.9(e)-359.7(to)-351(cl)18.4(as)19.6(si)17.7(ca)14.7(l)-356(v)0(o)15.5(l)0(-)]TJ 0 -1.0471 TD [(ta)18.4(ge)15.1(-d)19.6(ep)15.1(en)20.8(de)15.1(nt)-385.2(ca)14.7(l)13.9(c)0(i)12.8(u)0(m)-385.9(c)0(h)20.8(a)0(n)15.1(n)0(e)15.1(l)-390.1(an)15.1(ta)18.4(go)15.5(ni)18.9(st)17.7(s,)-383.6(in)-385.2(ad)15.1(di)18.9(ti)16.5(on)15.5(,)]TJ 0 -1.0528 TD [(th)18.9(es)13.9(e)-319.8(a)0(g)15.1(e)0(n)15.1(t)13.9(s)-326.3(a)0(r)19.2(e)-325.5(po)15.5(or)-316.1(br)19.6(on)15.5(ch)20.8(od)15.5(il)16.5(at)18.5(or)19.6(s)-326.3([)0(6)19.6(8\26172].)]TJ /F6 1 Tf 7.5115 -2.4526 TD [(Chl)-7.8(oride)-336.3(chan)-7.6(nels)]TJ /F8 1 Tf -6.51 -1.8494 TD [(A)-425.8(l)0(a)18.4(r)20.4(ge)-417.3(nu)21.2(mb)18.1(er)-418.9(of)-412.8(ch)20.8(lo)13.2(ri)17.3(de)-411.7(ch)15.1(an)20.8(ne)15.1(ls)-414.8(ha)20.8(ve)-417.3(no)21.2(w)-425.8(b)0(e)20.8(e)0(n)]TJ -1.0015 -1.0528 TD [(id)18.9(en)15.1(ti)16.5(fi)17.3(ed)-366.1(an)20.8(d)-376.3(t)0(h)18.9(e)0(s)13.9(e)-371.1(fa)13.5(ll)-364.8(in)18.9(to)-368.1(th)18.9(re)13.5(e)-371.1(m)0(a)12(j)0(o)18.9(r)-366.6(gr)19.6(ou)15.5(pi)18.9(ng)21.2(s,)-366.5(vo)15.5(l-)]TJ 0 -1.0471 TD [(ta)18.4(ge)15.1(-s)18.4(en)15.1(si)17.7(ti)22.2(ve)-457.2(ch)15.1(l)13.9(o)0(r)14(i)0(d)18.9(e)-462.1(ch)15.1(an)20.8(ne)15.1(ls)-454.7(\(C)14.9(IC)20.6(-2)-458.4(to)-453.5(-5)19.6(\),)-458(vo)21.2(lu)13.2(me)17.7(-)]TJ 25.1977 66.1583 TD [(re)13.5(gu)21.2(la)12.8(t)13.9(e)0(d)-383.2(c)0(h)20.8(l)0(o)13.2(r)0(i)17.3(d)0(e)-377.5(c)0(h)15.1(a)0(n)20.8(n)0(e)15.1(l)0(s)-380.7(a)0(n)20.8(d)-387.7(an)15.1(ot)18.8(he)15.1(r)-377.9(g)0(r)19.6(o)0(u)15.5(p)-387.7(in)18.9(cl)18.4(ud)15.5(in)18.8(g)]TJ 0 -1.0471 TD [(th)13.2(e)-570.2(c)0(y)15.1(s)0(t)17.7(i)0(c)-567.7(f)0(i)17.3(b)0(r)19.6(o)0(s)14.4(i)0(s)-562.8(t)0(r)17.3(a)0(n)15.1(s)0(m)16.9(e)0(m)17.7(b)0(r)19.6(a)0(n)15.1(e)-575.9(co)20.8(nd)15.5(uc)20.8(ta)12.8(nc)20.8(e)-575.9(r)0(e)19.2(g)0(u)15.5(l)0(a)18.4(-)]TJ 0 -1.0528 TD [(to)13.2(r)-304(a)0(n)20.8(d)-308.1(th)18.9(e)-302.8(c)0(a)14.7(l)0(c)18.4(i)0(u)18.8(m)0(-)16.5(a)0(c)14.7(t)0(i)16.5(v)0(a)20.8(t)0(e)12.8(d)-302.4(ch)15.1(lo)18.9(ri)17.3(de)-297.8(ch)20.8(an)15.1(ne)20.8(l.)-299.4(R)11.6(e)0(l)18.4(a)0(t)12.8(i)0(v)18.8(e)0(l)18.4(y)]TJ 0 -1.0471 TD [(li)16.5(tt)16.5(le)-203.5(wo)17.3(rk)-208(ha)20.8(s)-212.5(b)0(e)15.1(e)0(n)-206.8(c)0(a)20.4(r)0(r)18(i)0(e)12.8(d)-211.3(ou)21.2(t)-213.7(o)0(n)-206.4(c)0(h)20.8(l)0(o)13.2(r)0(i)17.3(d)0(e)-201.1(c)0(h)15.1(a)0(n)20.8(n)0(e)15.1(l)-213.7(ex)20.8(pr)13.9(es)19.6(-)]TJ 0 -1.0528 TD [(si)17.7(on)-121(i)13.9(n)-126(ai)18.4(rw)15.7(ay)-115.7(sm)11.2(oo)21.2(th)-117.7(mu)18.1(sc)19.6(le)12.8(,)-119.9(a)0(l)12.8(t)0(h)18.8(o)0(u)21.2(g)0(h)-121(a)0(i)18.5(r)0(w)15.7(a)0(y)-115.7(s)0(m)16.9(o)0(o)21.2(t)0(h)-117.7(m)0(u)18.1(s)0(-)]TJ 0 -1.0471 TD [(cl)12.8(es)-424.2(ex)20.8(pr)13.9(es)19.6(s)-434.4(a)-433.7(ca)14.7(lc)18.4(iu)18.9(m-)16.5(ac)14.7(ti)22.2(va)15.1(te)18.4(d)-433.2(c)0(h)15.1(l)0(o)18.8(r)0(i)17.3(d)0(e)-423(c)0(u)15.1(r)0(r)18(e)0(n)15.1(t)0(.)-424.6(T)12.2(he)15.1(se)]TJ 0 -1.0528 TD [(ch)15.1(an)15.1(ne)20.8(ls)-460.4(ac)20.4(ti)16.5(va)15.1(te)-459.6(br)19.6(ie)18.4(fl)17.3(y)-467.4(f)0(o)13.9(l)0(l)16.5(o)0(w)17.3(i)0(n)18.9(g)-467.4(in)18.8(tr)17.3(ac)14.7(el)18.5(lu)18.9(la)18.4(r)-469(c)0(a)14.7(l)0(c)18.4(i)0(u)18.8(m)]TJ 0 -1.0471 TD [(re)13.5(le)18.4(as)19.6(e)-325.5(b)0(u)21.2(t)-327.5(ar)19.2(e)-319.8(r)0(a)13.5(p)0(i)18.9(d)0(l)18.9(y)-325.1(ph)21.2(os)14.4(ph)21.2(or)14(yl)18.9(at)18.4(ed)-314.9(by)-314.5(ca)20.4(lc)18.4(iu)13.2(m/)21.4(ca)14.7(lm)15.7(o-)]TJ 0 -1.0527 TD [(du)15.5(li)16.5(n-)19.6(de)15.1(pe)20.8(nd)15.5(en)20.8(t)-230.8(p)0(r)19.6(o)0(t)18.9(e)0(i)12.8(n)-222.7(ki)18.8(na)15.1(se)19.6(,)-228(t)0(h)18.8(u)0(s)-219(l)0(e)18.4(a)0(d)15.1(i)0(n)18.9(g)-228.4(to)-214.5(un)15.5(co)20.8(up)15.5(li)16.5(ng)]TJ T* [(of)-310.4(th)18.9(e)-314.2(c)0(h)15.1(a)0(n)20.8(n)0(e)15.1(l)-316.1(fr)18(om)-306.3(re)13.5(gu)21.2(la)18.4(ti)16.5(on)-308.8(by)-303.1(cy)15.1(to)18.9(so)20(li)16.5(c)-319.8(c)0(a)20.4(l)0(c)18.5(i)0(u)13.2(m)-316.9([7)19.6(3].)]TJ /F6 1 Tf 7.2099 -3.1526 TD [(Pot)-8(assium)-341(channels)]TJ /F8 1 Tf -6.2084 -2.0998 TD [(As)-251.3(ha)15.1(s)-258(a)0(l)18.4(r)0(e)13.5(a)0(d)20.8(y)-262.5(be)20.8(en)-252.3(me)17.7(nt)18.9(io)13.2(ne)20.8(d,)-251.5(po)21.2(ta)18.4(ss)13.2(iu)18.9(m)-260(c)0(h)20.8(a)0(n)15.1(n)0(e)15.1(l)13.9(s)-263.7(a)0(r)19.2(e)]TJ -1.0015 -1.0471 TD [(al)12.8(so)-253.1(li)16.5(ke)20.8(ly)-260(to)-254.3(be)-252.3(im)15.7(po)15.5(rt)17.3(an)20.8(t)-264.9(i)0(n)-254.3(t)0(h)13.2(e)-262.9(co)20.8(nt)13.2(ro)19.6(l)-264.9(o)0(f)-253.5(m)0(e)12(m)13.2(br)13.9(an)20.8(e)-268.6(p)0(o)21.2(-)]TJ 0 -1.0527 TD [(te)12.8(nt)18.9(ia)18.4(l)-247.8(i)0(n)-237.2(a)0(i)18.5(r)0(w)15.7(a)0(y)-235.3(s)0(m)16.9(o)0(o)15.5(t)0(h)-237.2(m)0(u)18.1(s)0(c)13.9(l)0(e)-237.6(c)0(e)20.4(l)0(l)16.5(s)-246.7([7)19.6(4,)-251.5(75].)-254.6(Unde)-7.4(r)-258.4(rest-)]TJ 0 -1.0471 TD [(ing)-266.4(condition)-8.7(s,)-264.1(the)-261.2(mem)-9(brane)-262.3(p)-6.5(otential)-266.8(of)-264.9(airway)-269.4(smooth)]TJ 0 -1.0527 TD [(musc)-7.8(le)-220.6(cell)-8.6(s)-218.2(i)0(s)-227(remarkabl)-11.1(y)-222.7(constant)-229.1(due)-218.9(to)-225.8(strong)-226(outward)]TJ 0 -1.0471 TD [(recti)-11(fication.)-522.5(This)-522.9(is)-517.3(probably)-522.6(due)-514.8(to)-521.8(the)-517.2(presen)-8.2(ce)-514.5(of)]TJ 0 -1.0527 TD [(a)-433.7(delayed)-430(recti)-11(fier)-430.1(channel)-435.7([76].)-433.4(In)-429.9(addit)-9(ion,)-426.1(foll)-9.4(owing)]TJ 0 -1.0471 TD [(sti)-8.2(mulatio)-10.3(n)-353.6(with)-358.9(agents)-361.8(able)-359.1(to)-356.7(cause)-359(elevat)-10.6(ion)-357.5(of)-355.9(intra-)]TJ 0 -1.0527 TD [(cell)-8.6(ular)-178.2(cyclic)-181.3(AMP)-178.1(levels,)-182.4(the)-175.8(high-)-7.8(conduct)-8.5(ance)-175(calci)-9.8(um-)]TJ 0 -1.0471 TD [(sensi)-9(tive)-452.1(potas)-7.8(sium)-453.6(chann)-10.3(el)-448.2(is)-454.7(activated:)-462.6(as)-452.7(mentioned)]TJ 0 -1.0527 TD [(abo)-8.4(ve)-320.6(this)-322(is)-323.8(likely)-325.1(to)-322.6(be)-320.6(importan)-10.3(t)-316.1(i)0(n)-322.6(produci)-9.7(ng)-320.2(at)-323(least)]TJ 0 -1.0471 TD [(part)-229.4(of)-230.7(the)-227(relaxant)-229.9(respon)-7.8(se)-230.7(to)]TJ /F7 1 Tf 12.3485 0 TD (b)Tj /F8 1 Tf 7.472 0 0 6.641 437.839 508.422 Tm (2)Tj 9.963 0 0 9.963 441.581 510.123 Tm [(-agonists)-232.3([33\26135])-8.5(.)-222.3(A)97.7(TP-)]TJ -13.2761 -1.0528 TD [(sensi)-9(tive)-389.5(potas)-7.8(sium)-391(channel)-8.9(s)-388.9(\()0(K)]TJ 7.472 0 0 6.641 440.561 497.99 Tm -0.1034 Tc [(AT)-103.5(P)]TJ 9.963 0 0 9.963 453.827 499.634 Tm 0 Tc [(\))-389.3(are)-386(also)-394(presen)-8.2(t)-384.4(i)0(n)]TJ -14.5052 -1.0471 TD [(airw)-11.4(ay)-258(smooth)-261.7(musc)-7.8(le,)-260.8(althou)-9.7(gh)-257.6(the)-261.2(lack)-262.3(of)-259.2(effectiveness)]TJ 0 -1.0527 TD [(of)-458.4(acti)-8.6(vators)-459.7(of)-458.4(K)]TJ 7.472 0 0 6.641 384.831 477.071 Tm -0.1034 Tc [(AT)-103.5(P)]TJ 9.963 0 0 9.963 402.633 478.715 Tm 0 Tc [(such)-459.9(as)-452.7(levcr)-8.6(omaka)-7.8(lin)-456.6(or)-458.4(antag-)]TJ -9.3666 -1.0471 TD [(onist)-9.8(s)-360.5(o)0(f)-355.9(K)]TJ 7.472 0 0 6.641 354.954 466.583 Tm -0.1034 Tc [(AT)-103.5(P)]TJ 9.963 0 0 9.963 371.792 468.283 Tm 0 Tc [(such)-363.2(as)-361.6(glibenclam)-13.4(ide)]TJ /F4 1 Tf 9.3382 0 TD [(in)-362.4(vivo)]TJ /F8 1 Tf 3.1412 0 TD [(on)-360(airway)]TJ -18.7504 -1.0527 TD [(tone)-256.2(imp)-7.8(ly)-254.3(that)-258.6(K)]TJ 7.472 0 0 6.641 378.935 456.151 Tm -0.1034 Tc [(AT)-103.5(P)]TJ 9.963 0 0 9.963 394.696 457.795 Tm 0 Tc [(is)-255.5(unlikely)-258.3(to)-254.3(be)-258(critically)-261.3(imp)-7.8(ortant)]TJ -8.57 -1.0471 TD [(in)-402.3(the)-397.7(regul)-8.2(ation)-401.6(of)-395.8(contr)-8.2(actile)-405.6(or)-395.8(relax)-8.6(ant)-397.7(respon)-7.8(ses)-397.7(in)]TJ 0 -1.0528 TD [(airw)-11.4(ay)-286.5(smooth)-290.1(musc)-7.8(le)-288.8([77].)-291.1(Recent)-291.7(mol)-7.8(ecular)-294.3(studies)-291.7(on)]TJ T* [(the)-249.8(natur)-8.2(e)-245.9(o)0(f)-247.8(the)-244.1(p)-6.5(otassium)-250.1(ch)-7.6(annel)-246(subuni)-8.1(ts)-249.8(expressed)-251.1(in)]TJ 0 -1.0471 TD [(airw)-11.4(ay)-428.7(myocy)-7.4(tes)-433.1(will)-435.2(help)-438.3(in)-430.7(defin)-8.2(ing)-431.5(the)-431.9(relative)-442.8(im-)]TJ 0 -1.0527 TD [(porta)-8.2(nce)-338.8(of)-333.2(these)-338.3(different)-335.9(channel)-8.9(s)-332([78,)-340(79].)]TJ /F6 1 Tf 8.1318 -3.1526 TD [(Other)-327.2(ch)-6.8(annels)]TJ /F8 1 Tf -7.1303 -2.0998 TD [(A)-215.2(l)0(a)18.4(r)20.4(ge)-201.1(nu)15.5(mb)18.1(er)-202.7(of)-202.3(so)20(di)18.9(um)-203.8(ch)20.8(an)15.1(ne)15.1(l)13.9(s)-212.5(ha)15.1(ve)-201.1(be)20.8(en)-201.1(id)18.9(en)15.1(ti)16.5(fi)17.3(ed)]TJ -1.0015 -1.0471 TD [(bu)15.5(t)-282(r)0(e)19.2(l)0(a)12.8(t)0(i)22.2(v)0(e)15.1(l)0(y)-271.4(l)0(i)16.5(t)0(t)16.5(l)0(e)-277.5(i)13.9(nf)13.9(or)19.6(ma)17.7(ti)16.5(on)-274.7(is)-272.6(av)15.1(ai)18.4(la)18.5(bl)18.9(e)-285.7(r)0(e)19.2(g)0(a)15.1(r)0(d)19.6(i)0(n)18.9(g)-285.3(th)18.8(ei)18.4(r)]TJ 0 -1.0527 TD [(ro)13.9(le)-328.7(\(i)17.3(f)-338.1(a)0(n)15.1(y)0(\))-327.5(i)0(n)-328.3(n)0(o)15.5(n)0(e)15.1(x)0(c)20.8(i)0(t)16.5(a)0(b)15.1(l)13.9(e)-342.6(c)0(e)20.4(l)0(l)16.5(s)-337.7(su)14.4(ch)-326.3(as)-333.2(ai)18.5(rw)15.7(ay)-326.3(sm)11.2(oo)21.2(th)]TJ 0 -1.0471 TD [(mu)12.4(sc)19.6(le)18.4(.)-250.8(I)0(n)-247.8(a)0(d)20.8(d)0(i)13.2(t)13.9(io)13.2(n,)-240.2(a)-251.6(n)0(o)15.5(n)0(s)20(e)0(l)12.8(e)0(c)20.4(t)0(i)16.5(v)0(e)-240.9(c)0(a)14.7(t)0(i)16.5(o)0(n)-240.5(c)0(u)15.1(r)0(r)18(e)0(n)15.1(t)-253.5(ha)20.8(s)-252.3(b)0(e)15.1(e)0(n)]TJ 0 -1.0528 TD 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[(4.)-1766.5(Hall)-397.8(IP)102.6(,)-401.3(W)32.8(iddop)-398.2(S,)-399.3(T)60.2(ownsend)-399(P)103.1(,)-401.3(Daykin)-400.7(K.)-397.7(Control)-405.2(of)]TJ 2.5165 -1.1318 TD [(cyclic)-216(AMP)-216(content)-222(in)-216.4(primary)-217.4(cultures)-217.4(of)-221.3(human)-214.1(tracheal)]TJ 0 -1.1255 TD [(smooth)-394.4(muscle)-394(cells.)]TJ /F4 1 Tf 8.9596 0 TD [(Br)-395.7(J)-397.6(Pharmacol)]TJ /F8 1 Tf 7.0248 0 TD [(1992;)-398.2(107:)-392.4(422\261)]TJ -15.9843 -1.1318 TD (428.)Tj -2.5165 -1.1128 TD [(5.)-1766.5(Y)98.4(ang)-377.6(CM,)-374(Chou)-375.7(S-P)104.6(,)-376(Sung)-375.9(T)85.5(-C,)-380.6(Chien)-377.4(H-J.)-373.6(Regulation)]TJ 2.5165 -1.1255 TD [(of)-373(functional)-388.3(muscarinic)-388.7(receptor)-391.6(expression)-385.9(in)-387.1(tracheal)]TJ 0 -1.1318 TD [(smooth)-388.1(muscle)-394(cells.)]TJ /F4 1 Tf 8.9532 0 TD [(Am)-391.5(J)-391.3(Physiol)]TJ /F8 1 Tf 5.9056 0 TD [(1991;)-391.9(261:)-392.4(C1)34.2(123\261)]TJ -14.8588 -1.1255 TD [(C1)34.2(129.)]TJ -2.5165 -1.1128 TD 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[(8.)-1766.5(Chopra)-337.5(LC,)-338.9(T)66.6(wort)-339.7(CHC,)-342.9(Cameron)-338.6(IR,)-336.4(W)70.8(ard)-334.3(JPT)67.8(.)-338(Inosi-)]TJ 2.5165 -1.1318 TD [(tol)-325.7(1,4,5-trisphosphate-)-331.1(and)-320.7(guanosine)-327.3(5)]TJ /F17 1 Tf 16.2309 0 TD (')Tj /F8 1 Tf 0.2213 0 TD (-)Tj /F4 1 Tf 0.6449 0 TD (0)Tj /F8 1 Tf 0.4995 0 TD (-\(3-thiophos-)Tj -17.5967 -1.1255 TD [(phate\)-induced)-441.2(Ca)]TJ 6.725 0 0 5.977 147.855 408.812 Tm 0.0001 Tc (2+)Tj 8.966 0 0 8.966 158.967 404.844 Tm 0 Tc [(release)-442.7(in)-437.7(cultured)-443.8(airway)-439.4(smooth)]TJ -8.713 -1.1318 TD (muscle.)Tj /F4 1 Tf 3.3828 0 TD [(Br)-332.5(J)-334.4(Pharmacol)]TJ /F8 1 Tf 6.8414 0 TD [(1991;)-334.9(104:)-329.1(901\261906.)]TJ -12.7407 -1.1128 TD [(9.)-1766.5(Kotlikof)11.6(f)-582.2(MI,)-585.2(Murray)-581(RK,)-585.3(Reynolds)-585.7(EE.)-577.9(Histaininc-)]TJ 2.5165 -1.1255 TD [(induced)-346.1(calcium)-343.8(release)-354.2(and)-339.7(phorbol)-347.5(antagonism)-350.1(in)-349.1(cul-)]TJ 0 -1.1318 TD [(tured)-411.6(airway)-420.4(smooth)-419.7(muscle)-412.9(cells.)]TJ /F4 1 Tf 14.5743 0 TD [(Am)-416.8(J)-410.3(Physiol)]TJ /F8 1 Tf 5.9752 0 TD (1987;)Tj -20.5495 -1.1255 TD [(253:)-329.1(C561\261C566.)]TJ -2.5165 -1.1128 TD [(10.)-1266.5(Daykin)-381.8(K,)-378.7(W)26.5(iddop)-379.2(S,)-380.4(Hall)-385.2(IP)102.6(.)-382.3(Control)-386.2(of)-379.3(histamine)-390.9(in-)]TJ 2.5165 -1.1318 TD [(duced)-237.3(inositol)-240.6(phospholipid)-236.2(hydrolysis)-243.3(in)-235.3(cultured)-241.5(human)]TJ 0 -1.1255 TD [(tracheal)-475(smooth)-476.6(muscle)-476.2(cells.)]TJ /F4 1 Tf 12.7849 0 TD [(Eur)-471.1(J)-473.5(Pharmacol)]TJ /F8 1 Tf 7.7645 0 TD (1993;)Tj -20.5495 -1.1318 TD [(246:)-329.1(135\261140.)]TJ -2.5165 -1.1128 TD [(1)32.1(1)0(.)-1298.6(Rof)14.8(fel)-374.7(AF)68.7(,)-369.6(Meurs)-373.1(H,)-372.4(Zaagsina)-375.4(J,)]TJ /F4 1 Tf 16.408 0 TD [(et)-374.2(al)]TJ /F8 1 Tf 1.8526 0 TD [(.)-369.6(Muscarinic)-374.9(ace-)]TJ -15.744 -1.1255 TD [(tylcholine)-358.1(receptors)-360.6(and)-358.7(control)-356(of)-360.4(smooth)-356.5(muscle)-362.3(tone.)]TJ /F4 1 Tf 0 -1.1318 TD [(T)52.5(r)30.9(ends)-334(in)-330.2(Pharmacol)-334.3(Sci)]TJ /F8 1 Tf 10.4012 0 TD [(1994;)-334.9(15:)-329.6(407\261408.)]TJ -12.9177 -1.1065 TD [(12.)-1266.5(Janssen)-322(JL,)-329(Danial)-327(EE.)-325(Pre-)-333.4(and)-320.7(post-junctional)-334.7(muscar-)]TJ 2.5165 -1.1318 TD [(inic)-287(receptors)-297.4(in)-292.2(caninebronchi.)]TJ /F4 1 Tf 12.8861 0 TD [(Am)-290.3(J)-290.1(Physiol)]TJ /F8 1 Tf 5.6021 0 TD [(1990;)-290.7(259:)]TJ -18.4882 -1.1318 TD (L304\261L314.)Tj -2.5165 -1.1065 TD [(13.)-1266.5(W)77.1(atson)-285.3(N,)-277.6(Barnes)-281.6(PJ,)-279.9(Maclagan)-282.6(J.)-281.8(Actions)-283.7(of)-278.2(methoctra-)]TJ 2.5165 -1.1318 TD [(mine,)-238.8(a)-239.6(muscarinic)-243.3(M)]TJ 6.725 0 0 5.977 157.946 232.044 Tm (2)Tj 8.966 0 0 8.966 163.446 233.518 Tm [(receptor)-246.1(antagonist,)-239.6(on)-239.3(muscarinic)]TJ -9.2125 -1.1255 TD [(and)-225.9(nicotinic)-232.1(cholinoceptors)-229.1(in)-229(guinea-pig)-234.1(airways)]TJ /F4 1 Tf 20.1701 0 TD [(in)-229(vivo)]TJ /F8 1 Tf -20.1701 -1.1318 TD (and)Tj /F4 1 Tf 1.7641 0 TD [(in)-336.5(vitr)27.9(o)]TJ /F8 1 Tf 2.9402 0 TD (.)Tj /F4 1 Tf 0.5817 0 TD [(Br)-332.5(J)-334.4(Pharmacol)]TJ /F8 1 Tf 6.8414 0 TD [(1992;)-334.9(105:)-335.5(107\2611)34.2(12.)]TJ -14.6439 -1.1128 TD [(14.)-1266.5(Y)98.4(ang)-523.1(CM,)-525.8(Chou)-521.2(S-P)104.6(,)-521.4(W)70.8(ang)-523.1(Y)104.7(-)0(Y)123.2(,)-521.4(Hsieh)-522.6(J-T)71.7(,)-521.4(Ong)-526.6(R.)]TJ 2.5165 -1.1255 TD [(Muscarinic)-280(regulation)-287.1(of)-284.5(cytosolic)-281.5(free)-284(calcium)-286.9(in)-279.6(canine)]TJ 0 -1.1318 TD [(tracheal)-266.3(smooth)-274.3(muscle)-267.5(cells:)-276.7(Ca)]TJ 6.725 0 0 5.977 198.198 187.03 Tm 0.0001 Tc (2+)Tj 8.966 0 0 8.966 207.779 183.061 Tm 0 Tc [(requirement)-274.2(for)-266(phos-)]TJ -14.157 -1.1255 TD [(pholipase)-228.5(C)-231.9(activation.)]TJ /F4 1 Tf 9.3073 0 TD [(Br)-231.3(J)-233.2(Pharmacol)]TJ /F8 1 Tf 6.5379 0 TD [(1993;)-233.8(1)32.1(10:)-228.5(1239\261)]TJ -15.8452 -1.1318 TD (1247.)Tj -2.5165 -1.1128 TD [(15.)-1266.5(Abela)-268.2(A,)-264.9(Daniel)-270.1(EE.)-261.8(Neural)-275(and)-263.8(myogenic)-265.3(effects)-260.5(of)-271.8(leu-)]TJ 2.5165 -1.1255 TD [(kotrienes)-242.2(C)]TJ 6.725 0 0 5.977 121.436 141.222 Tm (4)Tj 8.966 0 0 8.966 124.838 142.753 Tm 0.2369 Tc (,D)Tj 6.725 0 0 5.977 135.666 141.222 Tm 0 Tc (4)Tj 8.966 0 0 8.966 141.165 142.753 Tm [(and)-244.9(E)]TJ 6.725 0 0 5.977 161.631 141.222 Tm (4)Tj 8.966 0 0 8.966 167.187 142.753 Tm [(on)-239.3(canine)-238.9(bronchial)-247.3(smooth)-242.7(mus-)]TJ -9.6298 -1.1318 TD (cle.)Tj /F4 1 Tf 1.7262 0 TD [(Am)-334.6(J)-334.4(Physiol)]TJ /F8 1 Tf 5.7286 0 TD [(1994;)-328.6(266:)-335.5(L414\261L425.)]TJ -9.9712 -1.1128 TD [(16.)-1266.5(Panettieiri)-498.4(RA,)-490.4(Murray)-492.5(RK,)-496.8(DePalo)-493.9(LR,)-490.6(Y)92(advish)-493.5(P)84.1(A)0(,)]TJ 2.5165 -1.1255 TD [(Kotlikof)11.6(f)-373.5(MI.)-370.3(A)-369.5(human)-372.2(airway)-369.9(smooth)-375.4(muscle)-368.7(cell)-375.3(line)]TJ 27.9978 73.5671 TD [(that)-407.2(retains)-413.9(physiological)-414.6(responsiveness.)]TJ /F4 1 Tf 17.2742 0 TD [(Am)-410.5(J)-410.3(Physiol)]TJ /F8 1 Tf -17.2742 -1.1381 TD [(1989;)-334.9(256:)-329.1(C329\261C335.)]TJ -2.5165 -1.1128 TD [(17.)-1266.5(Farmer)-308.7(SG,)-307.3(Ensore)-312.2(JE,)-303.7(Burch)-312.7(RM.)-304.5(Evidence)-310.9(that)-312.3(cultur)10.2(-)]TJ 2.5165 -1.1381 TD [(ed)-245.4(airway)-249.7(smooth)-249(muscle)-248.5(cells)-249.6(contain)-247.3(bradykinin)-247(B)]TJ 6.725 0 0 5.977 518.003 740.296 Tm (2)Tj 8.966 0 0 8.966 523.616 741.77 Tm (and)Tj -21.3841 -1.1381 TD (B)Tj 6.725 0 0 5.977 337.833 730.034 Tm (3)Tj 8.966 0 0 8.966 344.466 731.565 Tm (receptors.)Tj /F4 1 Tf 4.23 0 TD [(Am)-366.2(J)-366(Respir)-365.4(Cell)-367.6(Mol)-368(Biol)]TJ /F8 1 Tf 11.4129 0 TD [(1991;)-366.6(4:)-368.1(273\261)]TJ -17.0466 -1.1381 TD (277.)Tj -2.5165 -1.1128 TD [(18.)-1266.5(Marsh)-575.5(KA,)-583.9(Hill)-577.5(SJ.)-577(Bradykinin)-580.5(B)]TJ 6.725 0 0 5.977 465.959 709.908 Tm (2)Tj 8.966 0 0 8.966 469.36 711.382 Tm [(-receptor-med)5.7(iated)]TJ -15.3331 -1.1381 TD [(phosphoinositide)-414.5(hydrolysis)-414(in)-412.4(bovine)-416.4(cultured)-418.5(tracheal)]TJ T* [(smooth)-394.4(muscle)-400.3(cells.)]TJ /F4 1 Tf 8.9659 0 TD [(Br)-389.4(J)-397.6(Pharmacol)]TJ /F8 1 Tf 7.0247 0 TD [(1992;)-391.9(107:)-398.7(443\261)]TJ -15.9906 -1.1381 TD (447.)Tj -2.5165 -1.1128 TD [(19.)-1266.5(Y)92(ang)-415.6(CM,)-411.9(Y)92(o)-416.8(Y)104.7(-L,)-417.3(Hsich)-415.1(J-T)71.7(,)-420.2(Ong)-412.8(R.)-418.1(5-Hydroxytryp-)]TJ 2.5165 -1.1381 TD -0.0001 Tc [(tamine)-319.4(receptor-mediated)-322.1(phosphoinositide)-319.8(hydrolysis)-319.3(in)]TJ T* 0 Tc [(canine)-295.8(cultured)-304.7(tracheal)-297.9(smooth)-299.6(muscle)-299.1(cells.)]TJ /F4 1 Tf 18.4945 0 TD [(Br)-300.8(J)-296.5(Phar-)]TJ -18.4945 -1.1444 TD (macol)Tj /F8 1 Tf 2.7568 0 TD [(1994;)-334.9(1)32.1(1)32.1(1)0(:)-336.5(777\261786.)]TJ -5.2733 -1.1065 TD [(20.)-1266.5(Murray)-505.2(RK,)-503.1(Kotlikoff)-501(MI.)-503(Receptor-activated)-504.9(calcium)]TJ 2.5165 -1.1381 TD [(influx)-388.4(in)-387.1(human)-391.1(airway)-388.8(smooth)-394.4(muscle)-387.6(cells.)]TJ /F4 1 Tf 19.0256 0 TD [(J)-391.3(Physiol)]TJ /F8 1 Tf -19.0256 -1.1444 TD [(1991;)-334.9(435:)-329.1(123\261144.)]TJ -2.5165 -1.1065 TD [(21.)-1266.5(Murray)-423(RK,)-414.6(Fleischmann)-423.8(BK,)-420.9(Kotlikoff)-412.4(MI.)-420.9(Receptor)9.4(-)]TJ 2.5165 -1.1381 TD [(activated)-292.5(Ca)-288(influx)-287.2(in)-292.2(human)-290(airway)-287.7(smooth)-286.9(muscle:)-294.7(use)]TJ 0 -1.1444 TD [(of)-208.6(Ca)-212.1(imaging)-205.2(and)-213.2(perforated)-208.2(patch-clamp)-216.1(techniques.)]TJ /F4 1 Tf 21.4979 0 TD (Am)Tj -21.4979 -1.1381 TD [(J)-334.4(Physiol)]TJ /F8 1 Tf 4.072 0 TD [(1993;)-334.9(264:)-329.1(C485\261C490.)]TJ -6.5885 -1.1065 TD [(22.)-1266.5(Hofmann)-476.6(T)72.9(,)-477.1(Obukhov)-473.9(AG,)-476.4(Schaefer)-476.1(M,)-477.3(Harteneck)-475.4(C,)]TJ 2.5165 -1.1381 TD [(Gudermann)-506.9(T)72.9(,)-502.4(Schultz)-511.5(G.)-498.9(Direct)-511.3(activation)-509.6(of)-505.8(human)]TJ /F4 1 Tf 0 -1.1445 TD (TRPC6)Tj /F8 1 Tf 3.3322 0 TD (and)Tj /F4 1 Tf 1.84 0 TD (TRPC3)Tj /F8 1 Tf 3.3322 0 TD [(channels)-403.5(by)-410(diacylglycerol.)]TJ /F4 1 Tf 11.5836 0 TD [(Natur)25.9(e)]TJ /F8 1 Tf -20.0879 -1.1381 TD [(1999;)-334.9(397:)-329.1(259\261263.)]TJ -2.5165 -1.1065 TD [(23.)-1266.5(Wheatley)-347(AP)100.3(,)-344.4(Hall)-347.2(IP)102.6(.)-350.7(Expression)-345.3(of)-347.7(homologues)-347.9(of)-347.7(the)]TJ 2.5165 -1.1445 TD [(transient)-427.9(receptor)-429.5(potential)-428.1(\(TRP\))-423.5(gene)-427.5(in)-425(primary)-426(cul-)]TJ 0 -1.1381 TD [(tured)-221.9(human)-220.4(airway)-224.4(smooth)-223.7(muscle)-223.2(cells.)]TJ /F4 1 Tf 16.5344 0 TD [(Br)-218.7(J)-226.9(Pharmacol)]TJ /F8 1 Tf -16.5344 -1.1381 TD [(1999;)-334.9(128:)-329.1(122.)]TJ -2.5165 -1.1128 TD [(24.)-1266.5(Hall)-328.3(IP)102.6(,)-331.7(Daykin)-331.2(K,)-328.2(W)32.8(iddop)-328.6(S.)]TJ /F7 1 Tf 15.0801 0 TD (b)Tj /F8 1 Tf 6.725 0 0 5.977 449.461 476.504 Tm (2)Tj 8.966 0 0 8.966 452.863 477.978 Tm [(-adrenoceptor)-332.8(desensil-)]TJ -13.4931 -1.1381 TD [(isation)-238.5(in)-235.3(cultured)-241.5(human)-233.1(airway)-237.1(smooth)-242.7(muscle.)]TJ /F4 1 Tf 19.6706 0 TD [(Clin)-235.1(Sci)]TJ /F8 1 Tf -19.6706 -1.1381 TD [(1993;)-334.9(84:)-329.6(151\261157.)]TJ -2.5165 -1.1128 TD [(25.)-1266.5(T)60.2(omlinson)-357.8(PR,)-352.9(W)32.8(ilson)-357.5(JW)82.7(,)-357(Stewart)-357.7(AG.)-362.6(Salbutamol)-356.1(in-)]TJ 2.5165 -1.1381 TD [(hibits)-365.7(the)-361(proliferation)-372.1(of)-366.7(human)-359.5(airway)-369.9(smooth)-362.8(muscle)]TJ T* [(cells)-483.5(grown)-482.3(in)-481.9(culture:)-490.4(relationship)-485.7(to)-481.9(elevated)-486.7(cAMP)]TJ T* (levels.)Tj /F4 1 Tf 2.8832 0 TD [(Biochem)-333.9(Pharmacol)]TJ /F8 1 Tf 8.5486 0 TD [(1995;)-334.9(49:)-336(1809\2611819.)]TJ -13.9483 -1.1128 TD [(26.)-1266.5(Pang)-268.2(L,)-271.5(Holland)-276.2(E,)-271.4(Knox)-266.8(AJ.)-271.9(Role)-276.7(of)-271.8(cyclo-oxygenase-2)]TJ 2.5165 -1.1381 TD [(induction)-280.5(in)-279.6(interleukin-1)]TJ /F7 1 Tf 10.1799 0 TD (b)Tj /F8 1 Tf 0.8283 0 TD [(induced)-276.6(attenuation)-287.8(of)-278.2(cultur)10.2(-)]TJ -11.0082 -1.1381 TD [(ed)-289.6(human)-290(airway)-294(smooth)-293.3(muscle)-292.8(cell)-293.1(cyclic)-291.9(AMP)-291.9(gener-)]TJ T* [(ation)-330.8(in)-330.2(response)-333.9(to)-330.2(isoprenaline.)]TJ /F4 1 Tf 13.7207 0 TD [(Br)-326.1(J)-328.1(Pharmacol)]TJ /F8 1 Tf 6.8287 0 TD (1998;)Tj -20.5495 -1.1381 TD [(125:)-335.5(1320\2611328.)]TJ -2.5165 -1.1128 TD [(27.)-1266.5(Barries)-284.4(PJ,)-286.2(Dixon)-287.7(CMS.)-283.6(The)-286.3(ef)12.9(fect)-285.4(of)-284.5(inhaled)-291.6(vasoactive)]TJ 2.5165 -1.1381 TD [(intestinal)-222.5(peptide)-215.7(on)-220.3(bronchial)-222(hyperreactivity)-224.2(in)-216.4(man.)]TJ /F4 1 Tf 21.4979 0 TD (Am)Tj -21.4979 -1.1381 TD [(Rev)-330.3(Respir)-340.1(Dis)]TJ /F8 1 Tf 6.4367 0 TD [(1984;)-328.6(130:)-335.5(162\261166.)]TJ -8.9532 -1.1128 TD [(28.)-1266.5(O)]TJ /F17 1 Tf 3.2373 0 TD (')Tj /F8 1 Tf 0.215 0 TD [(Donnell)-250.9(M,)-249.7(Garippa)-255.5(RJ,)-254.4(Rinaldi)-248.3(N,)]TJ /F4 1 Tf 14.2076 0 TD [(et)-254.1(al)]TJ /F8 1 Tf 1.7262 0 TD [(.)-255.8(Ro25-1553:)-249.5(a)]TJ -16.8695 -1.1381 TD [(novel)-454.9(long-acting)-463.6(vasoactive)-455.2(intestinal)-462.8(peptide)-462.3(agonist.)]TJ T* [(Part)-246.3(1:)]TJ /F4 1 Tf 2.839 0 TD [(in)-248(vitr)27.9(o)]TJ /F8 1 Tf 3.0919 0 TD (and)Tj /F4 1 Tf 1.6819 0 TD [(in)-248(vivo)]TJ /F8 1 Tf 2.9022 0 TD [(bronchodilator)-248.1(studies.)]TJ /F4 1 Tf 9.32 0 TD [(J)-245.9(Phar-)]TJ -19.835 -1.1381 TD [(macol)-331.7(Exp)-336.9(Ther)]TJ /F8 1 Tf 6.8414 0 TD [(1994;)-334.9(270:)-329.1(1282\2611288.)]TJ -9.3579 -1.1128 TD [(29.)-1266.5(T)60.2(orphy)-226.1(TJ,)-234.2(Hall)-233.4(IP)102.6(.)-230.5(Cyclic)-227.3(AMP)-235(and)-232.2(the)-228.3(control)-235.9(of)-227.6(airway)]TJ 2.5165 -1.1381 TD [(smooth)-274.3(muscle)-280.1(tone.)]TJ /F4 1 Tf 8.517 0 TD (In)Tj /F8 1 Tf 0.822 0 TD [(:)-273.8(Raeburn)-279.9(D,)-277.6(Giembycz)-274.7(MA,)-277.8(eds.)]TJ -9.3389 -1.1381 TD [(Airways)-399.4(Smooth)-391.8(Muscle.)-395.7(Biochemical)-399.2(Control)-398.9(of)-392(Con-)]TJ T* [(traction)-326.1(and)-320.7(Relaxation.)-331.4(Basle,)-324.3(Birkhauser)-327.1(V)104.7(erlag,)-325.7(1994;)]TJ T* [(pp.)-330.7(215\261233.)]TJ -2.5165 -1.1128 TD [(30.)-1266.5(Y)92(ang)-282.8(CM,)-279.2(Chou)-287.2(S-P)104.5(,)-281.1(Sung)-281.1(TC.)-288.3(Muscarinic)-286.4(receptor)-284.1(sub-)]TJ 2.5165 -1.1381 TD [(types)-538.3(coupled)-535.8(to)-538.8(generation)-543.7(of)-537.4(diff)10.4(erent)-537.8(second)-541.5(mes-)]TJ T* [(sangers)-460.9(in)-463(isolated)-465.4(tracheal)-462.3(smooth)-464(muscle)-463.5(cells.)]TJ /F4 1 Tf 20.9288 0 TD [(Br)-465.2(J)]TJ -20.9288 -1.1445 TD (Pharmacol)Tj /F8 1 Tf 4.7485 0 TD [(1991;)-334.9(104:)-329.1(613\261618.)]TJ -7.265 -1.1065 TD [(31.)-1266.5(W)32.8(iddop)-335(S,)-336.1(Daykin)-331.2(K,)-334.5(Hall)-334.6(IP)102.6(.)-331.7(Expression)-339(of)-335.1(muscarinic)]TJ 2.5165 -1.1381 TD (M)Tj 6.725 0 0 5.977 339.817 182.098 Tm (2)Tj 8.966 0 0 8.966 346.79 183.628 Tm [(receptors)-404.9(in)-399.7(cultured)-405.9(human)-403.8(airway)-407.8(smooth)-400.7(muscle)]TJ -1.6629 -1.1444 TD (cells.)Tj /F4 1 Tf 2.3837 0 TD [(Am)-334.6(J)-334.4(Respir)-333.8(Cell)-336(Mol)-336.4(Biol)]TJ /F8 1 Tf 11.2232 0 TD [(1993;)-334.9(9:)-336.5(541\261546.)]TJ -16.1234 -1.1065 TD [(32.)-1266.5(Sankary)-349.6(RM,)-342.4(Jones)-347.4(CA,)-351.3(Madison)-348.2(JM,)-345.2(Brown)-347.9(JK.)-347.8(Mus-)]TJ 2.5165 -1.1381 TD [(carinic)-520(cholinergic)-514(inhibition)-525.3(of)-518.4(cyclic)-519.5(AMP)-519.5(accumu-)]TJ 0 -1.1445 TD [(lation)-313.7(in)-317.5(airway)-313(smooth)-318.5(muscle:)-313.6(role)-317.2(of)-316.1(a)-315.4(pertussis)-314.3(toxin)]TJ 0 -1.1381 TD [(sensitive)-225.8(protein.)]TJ /F4 1 Tf 6.9489 0 TD [(Am)-220.8(Rev)-222.8(Respir)-220(Dis)]TJ /F8 1 Tf 7.6381 0 TD [(1988;)-221.1(138:)-221.6(145\261150.)]TJ -17.1035 -1.1065 TD [(33.)-1266.5(Miura)-285.8(M,)-281.3(Belvisi)-281.1(MG,)-284.1(Stretton)-286.9(CD,)-281.8(Y)98.4(acoub)-287.9(MH,)-277.8(Barnes)]TJ 2.5165 -1.1444 TD [(PJ.)-804.7(Role)-807.8(of)-809.3(potassium)-813.6(channels)-808.2(in)-804.4(bronchodilator)]TJ 20.853 76.3871 TD [(1)32.1(125)]TJ 7.472 0 0 7.472 169.058 797.499 Tm 0.0001 Tc [(SECO)-9.1(ND)-331.7(MESSENG)-10.1(ERS,)-333(ION)-336(CHANN)-12.6(ELS)-333.9(AND)-334.5(AIR)44.5(W)102.5(A)88.3(Y)-336.6(SMOOTH)-341.9(MUSCLE)]TJ ET endstream endobj 33 0 obj << /ProcSet [/PDF /Text ] /Font << /F4 7 0 R /F6 9 0 R /F7 10 0 R /F8 11 0 R /F17 34 0 R >> /ExtGState << /GS2 12 0 R >> >> endobj 36 0 obj << /Length 19096 >> stream BT /F8 1 Tf 8.966 0 0 8.966 80.844 772.157 Tm 0 g /GS2 gs 0 Tc [(responses)-391.5(in)-393.4(human)-391.1(airways.)]TJ /F4 1 Tf 12.2222 0 TD [(Am)-391.5(Rev)-393.5(Respir)-390.7(Dis)]TJ /F8 1 Tf 8.3273 0 TD (1992;)Tj -20.5495 -1.1191 TD [(146:)-329.1(132\261136.)]TJ -2.5165 -1.1065 TD [(34.)-1266.5(Kume)-388.6(H,)-391.4(T)60.2(akai)-385.6(A,)-391.4(T)60.2(okuno)-389.5(H,)-391.4(T)60.2(omita)-389.6(T)72.9(.)-388.6(Regulation)-392(of)]TJ 2.5165 -1.1192 TD (Ca)Tj 6.725 0 0 5.977 90.709 746.135 Tm 0.0001 Tc (2+)Tj 8.966 0 0 8.966 97.852 742.167 Tm 0 Tc [(-dependent)-275.8(K)]TJ 6.725 0 0 5.977 146.268 746.135 Tm 0 Tw (+)Tj 8.966 0 0 8.966 152.504 742.167 Tm [(channel)-276.3(activity)-276.9(in)-279.6(tracheal)-272.6(myocytes)]TJ -7.9922 -1.1128 TD [(by)-327.8(phosphorylation.)]TJ /F4 1 Tf 8.3715 0 TD [(Natur)32.2(e)]TJ /F8 1 Tf 3.0603 0 TD [(1989;)-334.9(341:)-329.1(152\261154.)]TJ -13.9483 -1.1128 TD [(35.)-1266.5(Kume)-281.1(H,)-290.2(Hall)-284(IP)102.6(,)-287.4(W)77.1(ashabau)-287.8(RJ,)-286(T)60.2(akagi)-283.9(K,)-283.9(Kotlikoff)-279.7(MI.)]TJ /F7 1 Tf 2.5165 -1.1192 TD (b)Tj /F8 1 Tf 0.5501 0 TD [(-Adrener)11(gic)-285.2(agonists)-287.4(regulate)-279.2(K\(Ca\))-285.4(channels)-283.3(in)-285.9(airway)]TJ -0.5501 -1.1128 TD [(smooth)-495.6(muscle)-495.1(by)-498.5(cAMP-dependent)-497.3(and)-497.8(-independent)]TJ 0 -1.1192 TD (mechanisms.)Tj /F4 1 Tf 5.4756 0 TD [(J)-334.4(Clin)-336.2(Invest)]TJ /F8 1 Tf 5.4946 0 TD [(1994;)-334.9(93:)-336(371\261379.)]TJ -13.4868 -1.1065 TD [(36.)-1266.5(Kume)-236.9(H,)-233.3(Graziano)-242.2(MP)102.9(,)-236.9(Kotlikoff)-229.1(MI.)-237.5(Stimulatory)-245.4(and)-238.5(in-)]TJ 2.5165 -1.1192 TD [(hibitory)-326.5(regulation)-325(of)-328.7(calcium)-324.9(activated)-330.4(potassium)-326.7(chan-)]TJ 0 -1.1128 TD [(nels)-425(by)-422.6(guanine)-428.3(nucleotide-binding)-433(proteins.)]TJ /F4 1 Tf 18.7854 0 TD [(Pr)27.9(oc)-428.7(Natl)]TJ -18.7854 -1.1192 TD [(Acad)-330(Sci)-335.7(USA)]TJ /F8 1 Tf 6.07 0 TD [(1992;)-328.6(89:)-336(1)32.1(1051\2611)28.3(1055.)]TJ -8.5865 -1.1065 TD [(37.)-1266.5(Kume)-401.2(H,)-404(Kotlikof)11.6(f)-405.1(MI.)-401.9(Muscarinic)-406.5(inhibition)-405.2(of)-404.6(single)]TJ 2.5165 -1.1191 TD (K)Tj 6.725 0 0 5.977 87.25 630.765 Tm 0.0001 Tc (Ca)Tj 8.966 0 0 8.966 97.682 632.239 Tm 0 Tc [(channels)-327.6(in)-330.2(smooth)-331.2(muscle)-337.1(cells)-331.8(by)-327.8(a)-334.4(pertussis-sen-)]TJ -1.8779 -1.1128 TD [(sitive)-258(G)-255.7(protein.)]TJ /F4 1 Tf 6.677 0 TD [(Am)-258.7(J)-258.5(Physiol)]TJ /F8 1 Tf 5.5009 0 TD [(1991;)-259.1(261:)-259.6(C1204\261C1209.)]TJ -14.6944 -1.1128 TD [(38.)-1266.5(Jones)-290.5(TR,)-300.9(Charette)-296.5(L,)-296.7(Garcia)-300.1(ML,)-296.9(Kaczorowski)-295.7(GJ.)-297.2(Sel-)]TJ 2.5165 -1.1192 TD [(ective)-487.9(inhibition)-493.7(of)-493.1(relaxationof)-495.5(guinea-pig)-487(trachea)-498.4(by)]TJ 0 -1.1128 TD [(charybdotoxin,)-260.8(a)-258.5(potent)-260.7(Ca)]TJ 6.725 0 0 5.977 177.562 596.239 Tm 0.0001 Tc (++)Tj 8.966 0 0 8.966 187.427 592.271 Tm 0 Tc [(activated)-267.2(K)]TJ 6.725 0 0 5.977 228.132 596.239 Tm (+)Tj 8.966 0 0 8.966 234.255 592.271 Tm [(channel)-263.7(inhib-)]TJ -17.1098 -1.1191 TD [(itor)53.2(.)]TJ /F4 1 Tf 1.8905 0 TD [(J)-334.4(Pharmacol)-334.3(Exp)-336.9(Ther)]TJ /F8 1 Tf 9.6045 0 TD [(1990;)-334.9(255:)-329.1(697\261706.)]TJ -14.0116 -1.1065 TD [(39.)-1266.5(Felbel)-372.9(J,)-370.3(T)28.6(rockur)-371.7(B,)-373.8(Ecker)-374.5(T)72.9(,)-376(Landgraf)-373.9(W)83.4(,)-369.6(Hofmann)-375.4(F)71.5(.)]TJ 2.5165 -1.1192 TD [(Regulation)-322.5(of)-316.1(cytosolic)-325.8(calcium)-318.6(by)-321.5(cAMP)-316.4(and)-320.7(cGMP)-322.8(in)]TJ 0 -1.1128 TD [(freshly)-254.6(isolated)-250.4(smooth)-255.3(muscle)-254.9(cells)-255.9(from)-248.4(bovine)-252(trachea.)]TJ /F4 1 Tf 0 -1.1192 TD [(J)-328.1(Biol)-335(Chem)]TJ /F8 1 Tf 5.3998 0 TD [(1988;)-334.9(263:)-335.5(16764\26116771.)]TJ -7.9163 -1.1128 TD [(40.)-1266.5(Gunst)-402.7(SJ,)-400(Stropp)-403.5(JQ.)-404.7(Effec)10.2(t)-400.2(o)0(f)-404.6(Na-K)-403.6(adenosinetriphos-)]TJ 2.5165 -1.1128 TD [(phatase)-353.4(activity)-365.4(on)-353.1(relaxation)-362.7(of)-360.4(canine)-359.1(tracheal)-361.1(smooth)]TJ 0 -1.1191 TD (muscle.)Tj /F4 1 Tf 3.3828 0 TD [(J)-334.4(Appl)-332.6(Physiol)]TJ /F8 1 Tf 6.2787 0 TD [(1988;)-334.9(64:)-329.7(635\261641.)]TJ -12.1779 -1.1065 TD [(41.)-1266.5(Hulks)-579.7(G,)-581.1(Mohammed)-587.9(AF)75(,)-584.6(Jardine)-582.2(A,)-581.1(Connell)-587.4(JMC,)]TJ 2.5165 -1.1192 TD [(Thomson)-262.2(NC.)-262.8(Circulating)-268.4(plasma)-261.2(concentrations)-266.8(of)-265.5(atrial)]TJ 0 -1.1128 TD [(natriuretic)-555.3(peptide)-557.2(and)-554.7(catecholamines)-558.1(in)-557.8(response)-555.2(to)]TJ 0 -1.1191 TD [(maximal)-289(exercise)-296.7(in)-292.2(normal)-292.8(and)-289.1(asthmatic)-295.8(subjects.)]TJ /F4 1 Tf 20.9415 0 TD (Tho-)Tj -20.9415 -1.1128 TD (rax)Tj /F8 1 Tf 1.6503 0 TD [(1991;)-335(46:)-336(824\261828.)]TJ -4.1668 -1.1128 TD [(42.)-1266.5(Robichaud)-242.3(A,)-239.6(Michoud)-239.5(MC,)-241.2(Hamet)-244.8(P)103.1(,)-236.9(Du)-242.6(Souich)-244.3(P)103.1(.)-236.9(Plas-)]TJ 2.5165 -1.1192 TD [(ma)-259.9(atrial)-257.5(natriuretic)-264.4(peptide)-266.3(during)-259.5(spontaneous)-257.9(broncho-)]TJ 0 -1.1128 TD [(constriction)-333.9(in)-336.5(asthmatics.)]TJ /F4 1 Tf 10.8501 0 TD (Peptides)Tj /F8 1 Tf 3.7368 0 TD [(1995;)-334.9(16:)-329.6(653\261656.)]TJ -17.1035 -1.1128 TD [(43.)-1266.5(Hamad)-217.1(AM,)-220.8(Range)-216.7(S,)-216(Holland)-219.2(E,)-220.9(Knox)-216.2(AJ.)-221.4(Regulation)-221.3(of)]TJ 2.5165 -1.1128 TD [(cGMP)-461.9(by)-460.6(soluble)-463.7(and)-459.8(particulate)-465.6(guanylyl)-462(cyclases)-467.7(in)]TJ 0 -1.1192 TD [(cultured)-494.4(human)-498.6(airway)-502.6(smooth)-495.6(muscle.)]TJ /F4 1 Tf 17.0971 0 TD [(Am)-492.6(J)-498.8(Physiol)]TJ /F8 1 Tf -17.0971 -1.1128 TD [(1997;)-328.6(273:)-335.5(L807\261L813.)]TJ -2.5165 -1.1128 TD [(44.)-1266.5(Buga)-211.1(GM,)-220.8(Gold)-212.3(ME,)-214.7(W)70.8(ood)-213.5(KS,)-218.7(Chaudhuri)-218.2(G,)-214.4(Ignarro)-220.4(LJ.)]TJ 2.5165 -1.1128 TD [(Endothelium)-575.7(derived)-574.7(nitric)-573.9(oxide)-575(relaxes)-575.7(nonvascular)]TJ 0 -1.1192 TD [(smooth)-331.2(muscle.)]TJ /F4 1 Tf 6.6391 0 TD [(Eur)-338.3(J)-328.1(Pharmacol)]TJ /F8 1 Tf 7.3409 0 TD [(1989;)-334.9(161:)-335.5(61\26172.)]TJ -16.4965 -1.1128 TD [(45.)-1266.5(Y)98.4(oshihara)-316.2(S,)-310.8(Nadel)-318.8(JA,)-309.9(Figini)-318.8(M,)-312.9(Emanueli)-315.4(C,)-310.6(Pradelles)]TJ 2.5165 -1.1128 TD [(P)109.4(,)-325.4(Geppetti)-328.4(P)103.1(.)-319.1(Endogenous)-321.8(nitric)-327.3(oxide)-328.4(inhibits)-322.8(broncho-)]TJ 0 -1.1192 TD [(constriction)-239.1(induced)-238.6(by)-239.3(cold-air)-242.4(inhalation)-244.3(in)-235.3(guinea)-239.1(pigs.)]TJ /F4 1 Tf 0 -1.1128 TD [(Am)-328.2(J)-334.4(Respir)-333.8(Crit)-337.4(Car)27.2(e)-328.1(Med)]TJ /F8 1 Tf 11.6468 0 TD [(1998;)-334.9(157:)-335.5(547\261552.)]TJ -14.1633 -1.1128 TD [(46.)-1266.5(Figini)-325.1(M,)-331.9(Ricciardolo)-329(FL,)-326.4(Javdan)-332.8(P)109.4(,)]TJ /F4 1 Tf 17.4576 0 TD [(et)-329.9(al)]TJ /F8 1 Tf 1.8084 0 TD [(.)-325.4(Evidence)-329.9(that)]TJ -16.7494 -1.1128 TD [(endothelium-derived)-451.6(relaxing)-443.8(factor)-449.7(released)-448.5(by)-447.9(brady-)]TJ 0 -1.1192 TD [(kinin)-223.5(in)-229(the)-234.6(guinea)-226.5(pig)-228.5(trachea)-232.8(is)-230.2(nitric)-232.5(oxide.)]TJ /F4 1 Tf 18.0203 0 TD [(Am)-227.1(J)-226.9(Respir)]TJ -18.0203 -1.1128 TD [(Crit)-331.1(Car)27.2(e)-334.4(Med)]TJ /F8 1 Tf 6.3103 0 TD [(1996;)-328.6(153:)-335.5(918\261923.)]TJ -8.8268 -1.1128 TD [(47.)-1266.5(T)34.9(urner)-277.4(NC,)-281.8(Lamb)-275(J,)-275.5(W)70.8(orby)-277.1(A,)-277.6(Murray)-277.5(KJ.)-278.3(Relaxation)-284.3(of)]TJ 2.5165 -1.1192 TD [(guinea)-542.6(pig)-551(trachea)-549(by)-549.1(cyclic)-544.8(AMP)-551.1(phosphodiesterase)]TJ 0 -1.1128 TD [(inhibitors)-455.5(and)-459.8(their)-458.2(enhancement)-459.1(by)-460.6(sodium)-457.7(nitroprus-)]TJ 0 -1.1192 TD (side.)Tj /F4 1 Tf 2.1751 0 TD [(Br)-332.5(J)-334.4(Pharmacol)]TJ /F8 1 Tf 6.8414 0 TD [(1994;)-334.9(1)32.1(1)32.1(1)0(:)-330.2(1047\2611052.)]TJ -11.533 -1.1065 TD [(48.)-1266.5(Felbel)-372.9(J,)-370.3(T)28.6(rockur)-371.7(B,)-373.8(Ecker)-374.5(T)72.9(,)-376(Landgraf)-373.9(W)83.4(,)-369.6(Hofmann)-375.4(F)71.5(.)]TJ 2.5165 -1.1192 TD [(Regulation)-341.4(of)-347.7(cytosolic)-344.7(calcium)-343.8(by)-340.4(cyclic)-348.8(AMP)-342.5(and)-339.7(cy-)]TJ 0 -1.1128 TD [(clic)-400.6(GMP)-405.7(in)-399.7(freshly)-406.4(isolated)-408.5(smooth)-400.7(muscle)-406.6(cells)-407.6(from)]TJ 0 -1.1191 TD [(bovine)-327.9(trachea.)]TJ /F4 1 Tf 6.462 0 TD [(J)-334.4(Biol)-335(Chem)]TJ /F8 1 Tf 5.4061 0 TD [(1988;)-334.9(263:)-329.1(16764\26116771.)]TJ -14.3846 -1.1128 TD [(49.)-1266.5(Prakash)-262.3(YS,)-256.7(Kannan)-265.3(MS,)-260.4(Sieck)-257.2(GC.)-262.8(Nitric)-267.4(oxide)-258.9(inhibits)]TJ 2.5165 -1.1128 TD [(acetyl)-424.7(choline-induced)-435.8(intracellular)-429.9(calcium)-432.4(oscillations)]TJ 0 -1.1192 TD [(in)-374.4(porcine)-372.4(tracheal)-380.1(smooth)-375.5(muscle.)]TJ /F4 1 Tf 14.6944 0 TD [(Am)-378.8(J)-372.3(Physiol)]TJ /F8 1 Tf 5.855 0 TD (1997;)Tj -20.5495 -1.1128 TD [(272:)-329.1(L588\261L596.)]TJ -2.5165 -1.1128 TD [(50.)-1266.5(Kannan)-303.3(MS,)-298.3(Prakash)-306.5(YS,)-300.9(Johnson)-302.3(DE,)-305.8(Sieck)-301.5(GC.)-300.7(Nitric)]TJ 2.5165 -1.1128 TD [(oxide)-309.4(inhibits)-322.8(calcium)-312.2(release)-322.5(from)-317.9(sarcoplasmic)-319.1(reticul-)]TJ 0 -1.1192 TD [(um)-234.8(of)-240.2(porcine)-239.6(tracheal)-241(smooth)-236.3(muscle)-242.2(cells.)]TJ /F4 1 Tf 17.6156 0 TD [(Am)-239.7(J)-233.2(Physiol)]TJ /F8 1 Tf -17.6156 -1.1128 TD [(1997;)-328.6(272:)-335.5(L1\261L7.)]TJ -2.5165 -1.1128 TD [(51.)-1266.5(McGrogan)-430.4(I,)-433.3(Lu)-426.1(S,)-430.9(Hipworth)-438.2(S,)]TJ /F4 1 Tf 16.4775 0 TD [(et)-437.4(al)]TJ /F8 1 Tf 1.9095 0 TD [(.)-432.9(Mechanisms)-431.5(of)]TJ 12.1273 73.5671 TD [(cyclic)-494.2(nucleotide-induced)-499.7(relaxation)-495.5(in)-488.3(canine)-498.2(tracheal)]TJ 0 -1.1381 TD [(smooth)-331.2(muscle.)]TJ /F4 1 Tf 6.6454 0 TD [(Am)-334.6(J)-328.1(Physiol)]TJ /F8 1 Tf 5.7286 0 TD [(1995;)-328.6(268:)-335.5(L407\261L413.)]TJ -14.8905 -1.1128 TD [(52.)-1266.5(Jones)-435.9(KA,)-438.4(W)70.8(ong)-434.8(GY)127.2(,)-439.2(Jankowski)-439.5(M,)-433(Akao)-437.3(M,)-439.4(W)77.1(arner)]TJ 2.5165 -1.1381 TD [(DO.)-375.2(Cyclic)-372.7(GMP)-374.1(modulation)-370.4(of)-373(Ca)]TJ 6.725 0 0 5.977 463.975 745.738 Tm 0.0001 Tc (2+)Tj 8.966 0 0 8.966 474.463 741.77 Tm 0 Tc [(sensitivity)-375.2(in)-374.4(air)11(-)]TJ -15.9021 -1.1381 TD [(way)-305(smooth)-312.2(muscle.)]TJ /F4 1 Tf 8.5549 0 TD [(Am)-309.3(J)-309.1(Physiol)]TJ /F8 1 Tf 5.6527 0 TD 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466.242 670.79 Tm [(channels)-315(in)-317.5(porcine)]TJ -14.9853 -1.1381 TD [(tracheal)-399.1(smooth)-394.4(muscle)-400.3(cells.)]TJ /F4 1 Tf 12.4688 0 TD [(Am)-397.8(J)-397.6(Physiol)]TJ /F8 1 Tf 5.9182 0 TD [(1996;)-391.9(270:)]TJ -18.387 -1.1381 TD (L338\261L345.)Tj -2.5165 -1.1128 TD [(55.)-1266.5(Zhou)-399.8(H,)-404(T)60.2(orphy)-403.1(TJ.)-404.9(Relationship)-407.2(between)-406.1(cyclic)-405.7(GMP)]TJ 2.5165 -1.1381 TD [(accumulation)-299.2(and)-301.8(relaxation)-299.5(of)-297.1(canine)-295.8(trachealis)-306.8(induced)]TJ T* [(by)-372.1(nitrovasodilators.)]TJ /F4 1 Tf 8.6434 0 TD [(J)-372.3(Pharmacol)-372.3(Exp)-374.8(Ther)]TJ /F8 1 Tf 9.7626 0 TD [(1991;)-372.9(258:)]TJ -18.406 -1.1444 TD (972\261978.)Tj -2.5165 -1.1065 TD [(56.)-1266.5(Nakane)-214.5(M,)-211.7(Arai)-213(K,)-214.4(Saheki)-212.4(S,)-209.6(Kuno)-209.9(T)72.9(,)-211.6(Buechler)-218.3(W)83.4(,)-211.6(Murad)]TJ 2.5165 -1.1381 TD 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