Graber M L, Devine P
Division of Nephrology, VAMC, Northport, N.Y. 11768.
Ren Physiol Biochem. 1993 Sep-Oct;16(5):257-67. doi: 10.1159/000173771.
There is now convincing evidence that in addition to the vacuolar-type H(+)-ATPase, a gastric-type H+/K(+)-ATPase participates in acidification by the distal nephron. To determine whether a similar pump exists in the turtle bladder, we examined the dependence of acid secretion on mucosal K+, and the effects of supposedly specific inhibitors of the gastric H+/K(+)-ATPase, omeprazole and SCH 28080. In CO2-stimulated bladders both drugs produced dose-dependent inhibition of electrogenic H+ secretion measured as the reverse short-circuit current (RSCC). At the highest concentrations tested, H+ secretion decreased 45 +/- 16% with mucosal and 20 +/- 7% with serosal omeprazole (P < 0.01). SCH 28080 at 400 microM produced essentially complete inhibition of H+ secretion with either mucosal or serosal application. When H+ secretion was purposefully inhibited by DIDS or an adverse mucosal pH gradient, SCH 28080 had no effect on RSCC. Removing mucosal K+ (measured K+ < 50 microM), with or without mucosal barium, had no effect on RSCC. The inhibition of RSCC by omeprazole was reversed by mercaptoethanol. Finally, HCO3 secretion, as measured by either RSCC or pH-stat titration, increased significantly in response to 400 microM SCH 28080. The results demonstrate that these compounds inhibit acid secretion by the turtle bladder but stimulate the secretion of base. In view of the total independence of acid secretion on potassium, it is unlikely that any of the bladder's acid secretion is mediated by an H+/K(+)-ATPase. The most reasonable interpretation of the data is that omeprazole and SCH 28080, previously thought to be specific inhibitors of the H+/K(+)-ATPase, also inhibit the vacuolar H(+)-ATPase of the turtle bladder. The results also indicate that HCO3 secretion by the bladder employ a different mechanism of H+ transport than is used for acid secretion; there is no simple reversal of polarity in the acid- versus base-secreting cells.
现在有令人信服的证据表明，除了液泡型H(+)-ATP酶外，胃型H+/K(+)-ATP酶也参与远端肾单位的酸化过程。为了确定龟膀胱中是否存在类似的泵，我们研究了酸分泌对黏膜K+的依赖性，以及胃H+/K(+)-ATP酶的假定特异性抑制剂奥美拉唑和SCH 28080的作用。在二氧化碳刺激的膀胱中，这两种药物均产生剂量依赖性的对以反向短路电流（RSCC）衡量的电生性H+分泌的抑制作用。在测试的最高浓度下，黏膜应用奥美拉唑时H+分泌减少45±16%，浆膜应用时减少20±7%（P<0.01）。400微摩尔的SCH 28080在黏膜或浆膜应用时基本完全抑制H+分泌。当H+分泌被DIDS或不利的黏膜pH梯度有意抑制时，SCH 28080对RSCC无影响。去除黏膜K+（测量的K+<50微摩尔），无论有无黏膜钡，对RSCC均无影响。奥美拉唑对RSCC的抑制作用可被巯基乙醇逆转。最后，通过RSCC或pH计滴定测量，HCO3分泌在400微摩尔的SCH 28080作用下显著增加。结果表明，这些化合物抑制龟膀胱的酸分泌，但刺激碱分泌。鉴于酸分泌完全不依赖钾，膀胱的任何酸分泌不太可能由H+/K(+)-ATP酶介导。对数据最合理的解释是，先前被认为是H+/K(+)-ATP酶特异性抑制剂的奥美拉唑和SCH 28080，也抑制龟膀胱的液泡型H(+)-ATP酶。结果还表明，膀胱的HCO3分泌采用与酸分泌不同的H+转运机制；在酸分泌细胞和碱分泌细胞中不存在简单的极性反转。
