Competitive inhibition of p-aminohippurate transport by quinapril in rabbit renal basolateral membrane vesicles.
Competitive inhibition of p-aminohippurate transport by quinapril in rabbit renal basolateral membrane vesicles.
复制标题
喹那普利对兔肾基底外侧膜囊泡中对氨基马尿酸转运的竞争性抑制。
DOI：
10.1023/a:1023281325479
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Smith,DE
中科院分区：
文献类型：
--
作者：
Akarawut,W;Smith,DE
通过研究喹那普利对兔肾基底外侧膜囊泡（BLMV）转运对氨基马尿酸（PAH）的影响，探讨喹那普利与有机阴离子转运体相互作用的机制。顺式抑制研究表明，喹那普利是一种特异性和有效的PAH抑制剂。喹那普利的Km值约为20 μM，与丙磺舒相似，比PAH的Km值165 μM低8倍。尽管喹那普利导致反式抑制PAH的摄取在逆流研究，动力学研究表明，喹那普利是一种竞争性抑制剂PAH运输。后一项发现表明，喹那普利和PAH在转运蛋白上有共同的结合位点。总体而言，结果表明，喹那普利是一种高亲和力的抑制剂的有机阴离子转运蛋白在肾BLMV，药物相互作用可能发生与其他有机阴离子在近端细胞的基底外侧膜。
The mechanism of quinapril's interaction with the organic anion transporter was characterized by studying its effect on the transport ofp-aminohippurate (PAH) in rabbit renal basolateral membrane vesicles (BLMV). Cis-inhibition studies demonstrated that quinapril was a specific and potent inhibitor of PAH. TheKiof quinapril was about 20 μM, a value similar to that of probenecid and eight-times lower than theKmvalue of 165 μM 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 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.