| Detection of EETs and HETE-generating cytochrome P-450 enzymes and the effects of their metabolites on myometrial and vascular function. | |
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MedLine Citation:
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PMID: 19549792 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytochrome P-450 (CYP450) enzymes of the CYP2 and -4 family in humans metabolize arachidonic acid to generate bioactive epoxyeicosatrienenoic acids (EETs) and hydroxyeicosatetrenoic acids (HETEs). We report significantly higher levels of CYP 2J2 protein expression following the onset of labor (n = 6, P < 0.05), implying increased EET-generating capacity within the uterus. Myometrial relaxation to 8,9-EET and 5,6-EET was observed, with the latter being inhibited by preincubation with 1 muM paxilline and is supported by whole cell recordings showing a modest effect of 5,6-EET on myometrial outward-current density (n = 4, P < 0.05). Only 5,6-EET of the EETs tested affected vascular reactivity (n = 6). Both 12- and 20-HETE (n = 5-6) caused vasoconstriction of partially depolarized blood vessels, with glibenclamide (n = 5) enhancing the effect of 12-HETE alone. Our findings signify a role for CYP2C9/19, -2J2, and -4A11/22 in late pregnancy, possibly related to the synthesis of lipid metabolites and downstream effects on vascular remodeling in the term pregnant uterus. The presence of CYP4A11/22 and their resultant procontractile metabolites could argue either a role in the control and initiation of labor and/or modification of the vascular delivery system to influence blood flow to the laboring uterus. The differential effects of the EETs and HETEs in the pregnant human uterus identify the CYP pathway as a novel modulator of myometrial and vascular physiology during late pregnancy. |
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Authors:
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Timothy Pearson; Averil Y Warren; David A Barrett; Raheela N Khan |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-23 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 297 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-19 Completed Date: 2009-09-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E647-56 Citation Subset: IM |
Affiliation:
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Academic Division of Obstetrics & Gynecology, Univ. of Nottingham, The Medical School, Derby City General Hospital, Derby DE22 3DT, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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8,11,14-Eicosatrienoic Acid
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analogs & derivatives*,
metabolism,
pharmacology Blood Vessels / drug effects*, metabolism, physiology Cells, Cultured Cytochrome P-450 Enzyme System / analysis*, metabolism, physiology Eicosanoids / metabolism, pharmacology* Female Humans Hydroxyeicosatetraenoic Acids / metabolism, pharmacology* Labor, Obstetric / drug effects, metabolism, physiology Myometrium / blood supply, drug effects*, metabolism, physiology Pregnancy Uterine Contraction / drug effects, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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BBS/B/05125//Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/Eicosanoids; 0/Hydroxyeicosatetraenoic Acids; 7324-41-6/8,11,14-Eicosatrienoic Acid; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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