Competitive inhibition of p-aminohippurate transport by quinapril in rabbit renal basolateral membrane vesicles.
The mechanism of quinapril's interaction with the organic anion transporter was characterized by studying its effect on the transport of p-aminohippurate (PAH) in rabbit renal basolateral membrane vesicles (BLMV). Cis-inhibition studies demonstrated that quinapril was a specific and potent inhibitor of PAH. The Ki of quinapril was about 20 microM, a value similar to that of probenecid and eight-times lower than the K(m) value of 165 microM for PAH. Even though quinapril resulted in trans-inhibition of PAH uptake during counterflow studies, kinetic studies revealed that quinapril was a competitive inhibitor of PAH transport. This latter findings suggests that quinapril and PAH share a common binding site on the transporter. Overall, the results indicate that quinapril is a high-affinity inhibitor of the organic anion transporter in renal BLMV, and that drug-drug interactions may occur with other organic anions at the basolateral membrane of proximal cells.
Akarawut
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College of Pharmacy, University of Michigan, Ann Arbor 48109-0504, USA.
Smith
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism* / Q000648:ultrastructure; D008081:Liposomes; D008297:Male; D015394:Molecular Structure; D000077583:Quinapril; D011817:Rabbits; D044005:Tetrahydroisoquinolines; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D008081:Liposomes; D044005:Tetrahydroisoquinolines; D000077583:Quinapril; D010130:p-Aminohippuric Acid