Hormonal stimulation of 12(R)-HETE, a cytochrome P450 arachidonic acid metabolite in the rabbit cornea

Current Eye Research
K L DavisM L Schwartzman

Abstract

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. ...Continue Reading

References

Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M L SchwartzmanR C Murphy
Feb 1, 1974·British Journal of Pharmacology·P Bhattacherjee, K E Eakins
Mar 1, 1983·Experimental Eye Research·R N WilliamsK E Eakins
Mar 1, 1984·Current Eye Research·P S KulkarniB D Srinivasan

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Citations

Jan 1, 1996·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·B I Gaynes, R G Fiscella
Nov 1, 1993·Survey of Ophthalmology·K K Assil, A J Quantock

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