Regulation of the renal basolateral transport system for organic anions bycalcium channel blockers

Calcium channel blockers have been reported to exert multiple effects on re nal tubular function. Therefore, the effects of the calcium channel blocker s nifedipine and verapamil on the cellular uptake of tritiated para-aminohi ppuric acid (PAH) into microdissected non-perfused rabbit kidney S2 proxima l tubule segments were investigated to study a possible influence of calciu m channel blockers on renal PAH transport. Since the tubules were entirely collapsed, the accumulated radioactivity overwhelmingly reflects the transp ort across the basolateral membrane. Tubular PAH accumulation was increased by 1 and 10 mu M verapamil, and by 1 mu M nifedipine, but it was unaffecte d by lower or higher concentrations of these calcium channel blockers. The increase in PAH accumulation caused by 1 mu M nifedipine or 10 mu M verapam il was independent from changes in intracellular Ca2+ and inhibited by stau rosporine (1 and 10 nM) a potent inhibitor of protein kinase C (PKC). Our r esults indicate that the calcium channel blockers nifedipine and verapamil increase the transport of organic anions across the basolateral membrane of proximal tubules, probably by an activation of PKC. Furthermore, the incre ased tubular PAH transport may disturb the estimation of the renal PAH-clea rance. (C) 2000 Academic Press.