抽象的
钠通道抑制剂阻断囊性纤维化(CF)中增强的NA +重吸收。细胞外核苷酸促进通过Ca2 +门控Cl-通道的分泌物。这些效果的组合可以在CF中产生较少的粘性分泌物,其更容易咳出。该研究检测了在CF插入空突变小鼠(CFTR(TM1HGU)),Deltaf508纯合小鼠(CFTR(TM1CAM))和匹配对照动物中对鼻膜电位差(PD)与尿苷三磷酸酯(UTP)组合对尿苷三磷酸酯(PD)的影响。插入式CF小鼠和Deltaf508 CF小鼠中的中位数Pd分别为-28和-34 mV。这些值与对照动物(-20mV)显着不同。Amiloride和Loperamide在CFTR(TM1HGU)CF小鼠(分别分别的德雷普曲划线13mV&15mV)中降低了PD,表明NA +阻断。在无氯化物中加入UTP的后续加入PD(Deltapd -8 -12.5mV)。与CF插入空突变小鼠相比,Deltaf508小鼠表现出显着更大的反应(P <0.05)。UTP的作用简短而不延长加成的α-β-亚甲基 - 腺苷5'二磷酸。 Suramin, a competitive antagonist of P2 purinoceptors blocked the action of UTP. In conclusion, this study demonstrated dose dependant nasal membrane potential changes in differences mice with uridine triphosphate in the presence of sodium channel blockers suggestive of chloride secretion. More stable analogues of uridine triphosphate in combination with long acting sodium channel blockers such as loperamide may have therapeutic potential in cystic fibrosis.