Carrasquer G, Schwartz M
Department of Medicine (Nephrology), University of Louisville, Kentucky 40292, USA.
Proc Soc Exp Biol Med. 1996 Dec;213(3):258-61. doi: 10.3181/00379727-213-44057.
We have shown that polarization of an electrogenic H+/K+ ATPase pump located in the secretory (luminal) membrane of the frog gastric mucosa is the major factor contributing to the change in open circuit potential difference (OCPD) induced by voltage clamping. This transmucosal polarization was markedly reduced by H2 blockers famotidine and cimetidine, and by the H+/K+-ATPase inhibitors omeprazole and SCH 28080. SCN-, a nonspecific H+ secretion inhibitor, did not affect the polarization. In the present experiments, the effects of two other inhibitors of H+ secretion were examined, namely, acetazolamide (AA), a carbonic anhydrase inhibitor, and melittin (MEL), an inhibitor of the H+/K+-ATPase enzyme. When AA 10(-3) M or MEL 10(-5) M was added to the nutrient solution, H+ secretion was completely inhibited. While MEL markedly reduced the polarization induced by voltage clamp, AA did not affect the polarization. These data support the concept that MEL directly affects the electrogenic H+/K+-ATPase pump while the inhibition of H+ secretion by AA is by an indirect mechanism. The data further support the electrogenicity of the H+/K+-ATPase.
我们已经表明,位于蛙胃黏膜分泌(腔)膜上的生电H⁺/K⁺ATP酶泵的极化是导致电压钳制引起的开路电位差(OCPD)变化的主要因素。H₂受体阻滞剂法莫替丁和西咪替丁以及H⁺/K⁺-ATP酶抑制剂奥美拉唑和SCH 28080可显著降低这种跨黏膜极化。非特异性H⁺分泌抑制剂SCN⁻不影响极化。在本实验中,研究了另外两种H⁺分泌抑制剂的作用,即碳酸酐酶抑制剂乙酰唑胺(AA)和H⁺/K⁺-ATP酶抑制剂蜂毒素(MEL)。当将10⁻³M的AA或10⁻⁵M的MEL添加到营养液中时,H⁺分泌被完全抑制。虽然MEL显著降低了电压钳制引起的极化,但AA不影响极化。这些数据支持这样的概念,即MEL直接影响生电H⁺/K⁺-ATP酶泵,而AA对H⁺分泌的抑制是通过间接机制。这些数据进一步支持了H⁺/K⁺-ATP酶的生电性。