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 K-i of quinapril was about 20 mu M, a value similar to that of probenecid and eight-times lower than the K-m value of 165 mu M 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 finding suggests that quinapril and PAH share a common binding site an 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.