title: Cytochrome P450 metabolites of arachidonic acid: rapid incorporation and hydration of 14,15-epoxyeicosatrienoic acid in arterial smooth muscle cells.
abstract: Arachidonic acid is converted to epoxyeicosatrienoic acids (EETs) by cytochrome P450 monooxygenases. EETs produce arterial vasodilatation, and recent evidence suggests that they are endothelium-derived hyperpolarizing factors. In porcine coronary arteries contracted with a thromboxane mimetic agent, we find that relaxation is rapidly initiated by exposure to 14,15-EET. The relaxation slowly increases in magnitude, resulting in a response which is sustained for more than 10 min. Cultured porcine aortic smooth muscle cells rapidly take up [3H]14,15-EET. After 3 min, radioactivity is present in neutral lipids, phosphatidylcholine, and phosphatidylinositol. The cells also convert 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), and some DHET is detected in the medium after only 1 min of incubation. Like 14,15-EET, 14,15-DHET produces relaxation of the contracted coronary artery rings. These findings suggest that the incorporation into phospholipids and conversion to 14,15-DHET can occur at a rate that is fast enough to modulate the vasorelaxation produced by 14,15-EET.
authors.affiliation: Department of Biochemistry, College of Medicine, University of Iowa, Iowa City 52242, USA.
authors.forename: X
authors.initials: X
authors.lastname: Fang
authors.forename: T L
authors.initials: TL
authors.lastname: Kaduce
authors.forename: N L
authors.initials: NL
authors.lastname: Weintraub
authors.forename: A A
authors.initials: AA
authors.lastname: Spector
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry; D013552:Swine
chemical_list: C107016:14,15-dihydroxyeicosatrienoic acid; D006893:Hydroxyeicosatetraenoic Acids; D010743:Phospholipids; D016718:Arachidonic Acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D015126:8,11,14-Eicosatrienoic Acid