Cellular pH and water permeability control in frog urinary bladder. A possible action on the water pathway.

Mucosal acidification (from pH 8.1 to 6.0) reversibly inhibited the hydroosmotic responses to oxytocin, cyclic AMP and 8-bromo-cyclic AMP in frog urinary bladder. These inhibitory effects were only observed in the presence of a permeant buffer in the apical medium and could also be elicited by CO2 bubbling, even when the mucosal pH was clamped at 8.1. Acid pH reduced the oxytocin-induced net water flux faster than norepinephrine or oxytocin removal and the difference was especially important at low temperature. The time course of recovery from acid pH inhibition was, at 20 degree C, similar to that of the hormonal action, but when the medium temperature was reduced to 6-7 degrees C, the recovery from acid pH inhibition paradoxically became faster while the oxytocin action was markedly slowed down (t 1/2 of changes in net water fluxes (expressed in min): oxytocin addition at 20 degrees C, 6.2 +/- 0.9; at 6 degrees C, 24 +/- 3; oxytocin removal at 20 degrees C, 4.7 +/- 0.8; at 6 degrees C, 22 +/- 3; pH inhibition at 20 degrees C, 2.6 +/- 0.2, at 6 degrees C 2.5 +/- 0.2; recovery from pH 6 at 20 degrees C 6.5 +/- 0.9; at 6 degrees C, 2.7 +/- 0.3). These results can be explained by accepting two main loci sensitive to medium acidification: (1) the cyclase system and (2) an intracellular, temperature-independent, post-cyclic AMP site. The fact that the intramembranous particle aggregates associated with the oxytocin-induced water permeability increase did not disappear after the flow inhibition by acid pH at low temperature suggests that the second effect could be located at the water channel itself.