Document Detail


Ocular effects of a novel cytochrome P-450-dependent arachidonic acid metabolite.
MedLine Citation:
PMID:  2466808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Compound D is a novel arachidonic acid metabolite formed by a cytochrome P-450-dependent mono-oxygenase in bovine corneal epithelium. The structure of compound D was recently identified as 12-hydroxy-5,8,14-eicosatrienoic acid. In the current study, we described the biological properties and the ocular effects of this compound. Compound D is a potent vasodilator, and caused a dose-dependent relaxation of the rat tail artery preconstricted with phenylephrine with an EC50 of 1.5 microM, 4-5-fold more potent than acetylcholine. Topical application of as little as 10 ng of compound D onto the rabbit cornea produced a vasodilation of the conjunctival blood vessels. Intracameral injection of compound D (1-10 ng) caused a dose-dependent increase of up to 30-fold of the aqueous humor protein, indicating a breakdown of the blood-aqueous barrier. Compound D was also found to be a potent angiogenic factor, ie, it induced the appearance of new vessels in the cornea. The effects of 12-(R)-hydroxyeicosatrienoic acid (compound D) on the rabbit eye mimics the response of the eye to an inflammatory stimulus. We hypothesize, therefore, that ocular inflammation that occurs following injury to the cornea is mediated, at least in part, by the production of compound D by the corneal epithelium.
Authors:
J L Masferrer; R C Murphy; P J Pagano; M W Dunn; M Laniado-Schwartzman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  30     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  1989 Mar 
Date Detail:
Created Date:  1989-05-08     Completed Date:  1989-05-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  454-60     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, New York Medical College, Valhalla 10595.
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MeSH Terms
Descriptor/Qualifier:
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Animals
Aqueous Humor / metabolism
Arachidonic Acid
Arachidonic Acids / metabolism*
Arteries
Cattle
Chemical Phenomena
Chemistry
Conjunctiva / blood supply
Cytochrome P-450 Enzyme System / physiology*
Eye / drug effects*
Eye Proteins / metabolism
Hydroxyeicosatetraenoic Acids / pharmacology*,  physiology
Male
Neovascularization, Pathologic / physiopathology
Rats
Rats, Inbred Strains
Tail / blood supply
Vascular Resistance / drug effects
Grant Support
ID/Acronym/Agency:
EY-06513/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Eye Proteins; 0/Hydroxyeicosatetraenoic Acids; 506-32-1/Arachidonic Acid; 59985-28-3/12-Hydroxy-5,8,10,14-eicosatetraenoic 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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