Regulation of the renal basolateral transport system for organic anions by calcium channel blockers.
Calcium channel blockers have been reported to exert multiple effects on renal tubular function. Therefore, the effects of the calcium channel blockers nifedipine and verapamil on the cellular uptake of tritiated para -aminohippuric acid (PAH) into microdissected non-perfused rabbit kidney S2 proximal tubule segments were investigated to study a possible influence of calcium channel blockers on renal PAH transport. Since the tubules were entirely collapsed, the accumulated radioactivity overwhelmingly reflects the transport across the basolateral membrane. Tubular PAH accumulation was increased by 1 and 10 microm verapamil, and by 1 microm nifedipine, but it was unaffected by lower or higher concentrations of these calcium channel blockers. The increase in PAH accumulation caused by 1 microm nifedipine or 10 microm verapamil was independent from changes in intracellular Ca(2+) and inhibited by staurosporine (1 and 10 n m) a potent inhibitor of protein kinase C (PKC). Our results 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 increased tubular PAH transport may disturb the estimation of the renal PAH-clearance.
Hohage
H
H
Medizinische Poliklinik, Universitat Munster, Albert-Schweitzer-Strayse 33, Munster, D-48129, Germany.
Steinmetz
M
M
Mergelsberg
U
U
Löhr
M
M
Greven
J
J
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D011817:Rabbits; D010130:p-Aminohippuric Acid / Q000378:metabolism
D002121:Calcium Channel Blockers; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D002118:Calcium; D010130:p-Aminohippuric Acid