Competitive inhibition of p-aminohippurate transport by quinapril in rabbit renal basolateral membrane vesicles

Abstract

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.