环氧二十碳三烯酸对肾上皮细胞摄取⁸⁶Rb的影响。

Effects of epoxyeicosatrienoic acids on 86Rb uptake in renal epithelial cells.

作者信息

Staudinger R, Escalante B, Schwartzman M L, Abraham N G

机构信息

Department of Pharmacology, Rockefeller University, New York, New York 10021.

出版信息

J Cell Physiol. 1994 Jul;160(1):69-74. doi: 10.1002/jcp.1041600109.

DOI:10.1002/jcp.1041600109

PMID:8021300

Abstract

Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites formed endogenously via the cytochrome P450 pathway in rat, rabbit, and human kidney. We characterized the effects of the four regioisomeric EETs on ion transport in the renal epithelial cell line, LLC-PK1. Among the EETs, 14,15-EET was the most potent inhibitor of 86Rb uptake. Its effect was concentration-dependent (IC50 = 75 nM) and stereoselective to the 14S, 15R-EET. Experiments measuring 14,15-EET-induced 86Rb uptake inhibition in the presence of inhibitors of Na(+)-K(+)-ATPase activity (ouabain), Na(+)-K(+)-Cl- cotransporter (furosemide), and Na(+)-H+ exchanger (amiloride) suggested that 14,15-EET inhibits ion transport via an amiloride-sensitive mechanism. These results, together with previous reports demonstrating their endogenous production in the kidney, suggest an important role for EETs, specifically 14,15-EET, in the regulation of ion and water reabsorption in the kidney and implicate their function in renal pathophysiology.

摘要

环氧二十碳三烯酸（EETs）是通过细胞色素P450途径在大鼠、兔子和人类肾脏中内源性形成的花生四烯酸代谢产物。我们研究了四种区域异构体EETs对肾上皮细胞系LLC-PK1中离子转运的影响。在EETs中，14,15-EET是86Rb摄取的最有效抑制剂。其作用具有浓度依赖性（IC50 = 75 nM），且对14S, 15R-EET具有立体选择性。在存在Na(+)-K(+)-ATP酶活性抑制剂（哇巴因）、Na(+)-K(+)-Cl-协同转运蛋白抑制剂（呋塞米）和Na(+)-H+交换体抑制剂（阿米洛利）的情况下测量14,15-EET诱导的86Rb摄取抑制的实验表明，14,15-EET通过一种阿米洛利敏感机制抑制离子转运。这些结果，连同先前证明它们在肾脏中内源性产生的报告，表明EETs，特别是14,15-EET，在肾脏离子和水重吸收的调节中起重要作用，并暗示它们在肾脏病理生理学中的功能。