环孢素A在分离的肾近端小管细胞中的转运：钙通道阻滞剂的抑制作用。

Cyclosporine-A transport in isolated renal proximal tubular cells: inhibition by calcium channel blockers.

作者信息

Nagineni C N, Lee D B, Misra B C, Yanagawa N

机构信息

Division of Nephrology, VA Medical Center, Sepulveda, California 91343.

出版信息

Biochem Biophys Res Commun. 1988 Dec 30;157(3):1226-30. doi: 10.1016/s0006-291x(88)81005-2.

DOI:10.1016/s0006-291x(88)81005-2

PMID:2462869

Abstract

We have studied the transport characteristics of cyclosporine A (CSA) in isolated rabbit renal proximal tubular cells (PTC). The uptake as well as efflux was very rapid and dependent on temperature. PTC accumulated CSA by several fold above the incubation medium concentration. Kinetic analysis yielded an apparent Km and Vmax values of 5.1 microM and 47 Pmoles/10(6) cells/min respectively. Calcium channel blockers verapamil or diltiazem, at concentrations (0.5-1.0 mM) that inhibited calcium uptake, reduced CSA uptake significantly. Other calcium transport modulators A23187 (5 microM), trifluoroperazine (50 microM) and ruthenium red (100 microM) induced anticipated changes in calcium uptake but had no effect on CSA uptake. These results suggest a close association or interaction between the calcium channels and the CSA transporting/binding sites on PTC membranes.

摘要

我们研究了环孢素A（CSA）在分离的兔肾近端小管细胞（PTC）中的转运特性。摄取和流出都非常迅速，且依赖于温度。PTC将CSA积累至高于孵育培养基浓度数倍。动力学分析得出的表观Km和Vmax值分别为5.1微摩尔和47皮摩尔/10⁶细胞/分钟。钙通道阻滞剂维拉帕米或地尔硫䓬，在抑制钙摄取的浓度（0.5 - 1.0毫摩尔）下，显著降低了CSA摄取。其他钙转运调节剂A23187（5微摩尔）、三氟拉嗪（50微摩尔）和钌红（100微摩尔）引起了钙摄取的预期变化，但对CSA摄取没有影响。这些结果表明钙通道与PTC膜上的CSA转运/结合位点之间存在密切关联或相互作用。