Effect of acetazolamide and melittin on polarization of the frog gastric mucosa proton pump.

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.