Dibucaine stimulation of p-aminohippurate accumulation in rat kidney cortical slices

We studied the effects of dibucaine on p-aminohippurate (PAH) transport using rat kidney cortical slices. Addition of dibucaine in concentrations from 0.01 to 0.1 mM stimulated PAH accumulation in a concentration-dependent way; at higher concentrations, accumulation was inhibited. Kinetic studies showed that dibucaine increased the apparent maximal activity of PAH transport, whereas the apparent Km remained essentially constant. The efflux of PAH from the slices was significantly depressed by the drug. Dibucaine had no significant effect on the sodium gradient, medium to intracellular fluid. The drug had biphasic effects on hypotonic hemolysis; at lower concentrations (up to 0.2 mM) it protected erythrocytes, and at much higher concentrations, it has a lytic effect. The pattern of the membrane-stabilizing action of dibucaine was similar to that of the stimulation of PAH accumulation. These results indicate that dibucaine markedly stimulated accumulation of PAH. Stimulation by this drug of PAH transport cannot be explained by the increase in the sodium gradient; it may be due at least in part to membrane stabilization.