Document Detail

Hormonal stimulation of 12(R)-HETE, a cytochrome P450 arachidonic acid metabolite in the rabbit cornea.
MedLine Citation:
PMID:  2119938     Owner:  NLM     Status:  MEDLINE    
12(R)-HETE [12(R)-hydroxy-5, 8, 10, 14 eicosatetraenoic acid] is one of the major arachidonic acid metabolites produced by microsomal cytochrome P450 of the corneal epithelium. This metabolite is a potent inhibitor of Na(+)-K(+)-ATPase activity in several tissues. We investigated endogenous production of 12(R)-HETE in the rabbit corneal epithelium. Incubation of corneal epithelial sheets (prelabeled with 14C-arachidonic acid) with arginine vasopressin resulted in the production of radioactive 12(R)-HETE suggesting its formation from endogenously labeled-arachidonic acid. The maximal response was obtained with 1 microM arginine vasopressin and represents a 15-fold increase in 12(R)-HETE formation compared with that of control tissues. Stimulation of 14C-arachidonic acid release with a detergent, digitonin, also resulted in endogenous 12(R)-HETE formation. Analysis of the incubation media following digitonin treatment of prelabeled corneal epithelial sheets revealed that 12(R)-HETE production was maximal at 20 microM digitonin, a 17-fold increase over control values. This study is the first to describe hormonal and traumatic stimulation of 12(R)-HETE formation from endogenously labeled arachidonic acid in intact corneal tissues. This study demonstrates that the formation of this Na(+)-K(+)-ATPase inhibitor can be modulated by physiological and pathophysiological regulation.
K L Davis; M W Dunn; M L Schwartzman
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Current eye research     Volume:  9     ISSN:  0271-3683     ISO Abbreviation:  Curr. Eye Res.     Publication Date:  1990 Jul 
Date Detail:
Created Date:  1990-11-15     Completed Date:  1990-11-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8104312     Medline TA:  Curr Eye Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  661-7     Citation Subset:  IM    
Department of Pharmacology, New York Medical College, Valhalla.
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MeSH Terms
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Arachidonic Acid
Arachidonic Acids / metabolism*
Arginine Vasopressin / pharmacology
Chromatography, High Pressure Liquid
Cornea / drug effects,  enzymology,  metabolism*
Cytochrome P-450 Enzyme System / metabolism*
Digitonin / pharmacology
Epithelium / drug effects,  enzymology,  metabolism
Hydroxyeicosatetraenoic Acids / metabolism*
Grant Support
Reg. No./Substance:
0/Arachidonic Acids; 0/Hydroxyeicosatetraenoic Acids; 11024-24-1/Digitonin; 113-79-1/Arginine Vasopressin; 506-32-1/Arachidonic Acid; 59985-28-3/12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 9035-51-2/Cytochrome P-450 Enzyme System

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