Kanoh S, Kondo M, Tamaoki J, Kobayashi H, Motoyoshi K, Nagai A
Third Department of Medicine, National Defense Medical College, Saitama, Japan.
Am J Respir Cell Mol Biol. 2001 Sep;25(3):370-6. doi: 10.1165/ajrcmb.25.3.4382.
Adenosine 5'-triphosphate (ATP) stimulates airway epithelial Cl(-) secretion in a complicated manner. We examined the difference between ATP- and uridine 5'-triphosphate (UTP)-induced responses of short-circuit current (Isc) in bovine tracheal epithelium treated with amiloride. Each nucleotide caused an increase in Isc composed of the first and second peaks, where the second peak induced by ATP was higher compared with UTP. The ATP-induced second peak was inhibited by the protein kinase (PK) A inhibitor H89, saturation of P1 receptor with adenosine, and the P1 receptor antagonist 8-p-sulfophenyltheophylline, but not by the Ca(2+) chelator ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid plus the endoplasmic reticulum Ca(2+)-pump inhibitor thapsigargin, the adenosine breakdown enzyme adenosine deaminase, the ectonucleotidase inhibitor alpha,beta-methyleneadenosine 5'-diphosphate, or saturation of P2Y2 receptor with UTP. Thus, the response is associated with PKA-dependent pathway via P1-like receptor but not with Ca(2+)-dependent pathway via P2Y2 receptor, and ATP degradation products do not contribute to this response. Further, stimulation of cells with ATP increased PKA activity. In addition, pretreatment with glybenclamide, an inhibitor of cystic fibrosis transmembrane conductance regulator, reduced the second peak of Isc induced by ATP but was without effect on that induced by UTP. Therefore, ATP stimulates glybenclamide-sensitive Cl(-) secretion, and this action is partly mediated by PKA-dependent pathway via P1-like receptor.
腺苷5'-三磷酸（ATP）以复杂的方式刺激气道上皮细胞的氯离子（Cl⁻）分泌。我们研究了用氨氯吡咪处理的牛气管上皮细胞中，ATP和尿苷5'-三磷酸（UTP）诱导的短路电流（Isc）反应之间的差异。每种核苷酸都引起Isc增加，包括第一峰和第二峰，其中ATP诱导的第二峰比UTP诱导的更高。ATP诱导的第二峰被蛋白激酶（PK）A抑制剂H89、腺苷对P1受体的饱和作用以及P1受体拮抗剂8-对磺基苯基茶碱抑制，但不受Ca²⁺螯合剂乙二醇双（β-氨基乙醚）-N，N，N'，N'-四乙酸加内质网Ca²⁺泵抑制剂毒胡萝卜素、腺苷分解酶腺苷脱氨酶、胞外核苷酸酶抑制剂α，β-亚甲基腺苷5'-二磷酸或UTP对P2Y2受体的饱和作用抑制。因此，该反应通过P1样受体与PKA依赖性途径相关，而不是通过P2Y2受体与Ca²⁺依赖性途径相关，并且ATP降解产物对此反应没有贡献。此外，用ATP刺激细胞会增加PKA活性。另外，用囊性纤维化跨膜传导调节因子抑制剂格列本脲预处理可降低ATP诱导的Isc第二峰，但对UTP诱导的Isc第二峰没有影响。因此，ATP刺激格列本脲敏感的Cl⁻分泌，并且这种作用部分由通过P1样受体介导PKA依赖性途径介导。
