Inhibition of H+ secretion in the turtle bladder by colchicine and vinblastine

Abstract

In order to investigate a possible role of the microtubules in urinary acidification we measured H+ secretion by the turtle bladder in vitro before and after addition of either colchicine or vinblastine to the serosal phase. Both colchicine and vinblastine inhibited H+ secretion in a dose-dependent fashion; in the control hemibladders H+ secretion remained unchanged. The half-maximal inhibition of H+ secretion occurred at 5.2 x 10(-5) M for colchicine and 7.2 x 10(-6)M for vinblastine. The inhibitory effect of colchicine and vinblastine on H+ secretion was maximal at 10(-4)M and 5 x 10(-4)M, respectively. At these concentrations these compounds failed to alter SCC and resistance. The inhibition of H+ secretion by colchicine or vinblastine increased with time of exposure to the drugs. The effect of colchicine or vinblastine on H+ secretion was not reversible with removal of the drug or with addition of 5% CO2 in the serosal phase. Lumicolchicine, an isomer of colchicine devoid of capacity to interact with microtubules, failed to alter the rate of H+ secretion, suggesting that the observed effect of colchicine on H+ secretion was the result of disruption of microtubule function and not the consequence of nonspecific effect of the drug. These data provide evidence for a role of microtubules in urinary acidification by the turtle bladder in vitro, but an effect of these drugs on membrane-bound tubulin cannot be excluded.