PMID- 12570747
OWN - NLM
STAT- MEDLINE
DCOM- 20030326
LR  - 20191025
IS  - 1389-2002 (Print)
IS  - 1389-2002 (Linking)
VI  - 4
IP  - 1
DP  - 2003 Feb
TI  - Kidney CYP450 enzymes: biological actions beyond drug metabolism.
PG  - 73-84
AB  - 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.
FAU - Zhao, X
AU  - Zhao X
AD  - Department of Physiology, Medical College of Georgia, Augusta, Georgia 
      30912-2500, USA. xzhao@mail.mcg.edu
FAU - Imig, J D
AU  - Imig JD
LA  - eng
GR  - DK-38226/DK/NIDDK NIH HHS/United States
GR  - HL-59699/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Netherlands
TA  - Curr Drug Metab
JT  - Current drug metabolism
JID - 100960533
RN  - 0 (Pharmaceutical Preparations)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Cytochrome P-450 Enzyme System/*metabolism
MH  - Humans
MH  - Kidney/*enzymology/physiology
MH  - Pharmaceutical Preparations/*metabolism
MH  - Signal Transduction/physiology
RF  - 139
EDAT- 2003/02/07 04:00
MHDA- 2003/03/27 05:00
CRDT- 2003/02/07 04:00
PHST- 2003/02/07 04:00 [pubmed]
PHST- 2003/03/27 05:00 [medline]
PHST- 2003/02/07 04:00 [entrez]
AID - 10.2174/1389200033336892 [doi]
PST - ppublish
SO  - Curr Drug Metab. 2003 Feb;4(1):73-84. doi: 10.2174/1389200033336892.