Faculty Collaboration Database

Kidney CYP450 enzymes: biological actions beyond drug metabolism. Curr Drug Metab 2003 Feb;4(1):73-84

Date

02/07/2003

Pubmed ID

12570747

DOI

10.2174/1389200033336892

Scopus ID

2-s2.0-0037302804 (requires institutional sign-in at Scopus site)   86 Citations

Abstract

Arachidonic acid can be metabolized by cytochrome p450 (CYP450) enzymes to 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs), their corresponding dihydroxyeicosa-trienoic acids (DHETs), and 20-hydroxyeicosatetraenoic acid (20-HETE). These arachidonic acid metabolites are involved in the regulation of renal epithelial transport and vascular function. 20-HETE and EETs are produced in the renal microvascular smooth muscle cells and endothelial cells, respectively. 20-HETE constricts the preglomerular arterioles by inhibiting K(+) channels, and contributes importantly to renal blood flow autoregulatory responsiveness of the afferent arterioles. EETs dilate the preglomerular arterioles by activating the renal smooth muscle cell Ca(2+)-activated K(+) channels and hyperpolarizing smooth muscle cells. These EET actions are consistent with their identification as endothelium-derived hyperpolarizing factors (EDHFs). In the kidney, EETs and 20-HETE are also produced in the proximal tubule and the thick ascending loop of Henle, and these metabolites modulate ion transport in the proximal tubules and the thick ascending limb by inhibiting Na(+)-K(+)-ATPase and the Na(+)-K(+)-2Cl(-) cotransporter. CYP450 metabolites also act as second messengers for many paracrine and hormonal agents, including endothelin, nitric oxide, and angiotensin II. The production of kidney CYP450 arachidonic acid metabolites is altered in diabetes, pregnancy, hepatorenal syndrome, and in various models of hypertension, and it is likely that changes in this system contribute to the abnormalities in renal function that are associated with many of these conditions.

Author List

Zhao X, Imig JD

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acid
Cytochrome P-450 Enzyme System
Humans
Kidney
Pharmaceutical Preparations
Signal Transduction