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14, 15-cis-episulfide-eicosatrienoic acid, an 'epoxygenase' eicosanoid analog, inhibits ionophore- but not thrombin-induced platelet aggregation

K Bernstrom, K Malcolm, J McGee, J Maclouf, S Levy-Toledano, JR Falck and FA Fitzpatrick

Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.

An 'epoxygenase' eicosanoid analog, 14, 15-cis-episulfide- eicosatrienoic acid, has several unique pharmacological effects on platelets. These include (i) inhibition of ionophore A23187- but not thrombin-induced activation, (ii) inhibition of thromboxane B2 biosynthesis derived from endogenous but not exogenous arachidonic acid, and (iii) attenuation of ionophore-mediated increases in cytosolic Ca2+ when extracellular or membrane Ca2+ is available but not when these pools are excluded. Neither elevation of cyclic AMP levels, a potent inhibitory process, nor direct antagonism of the prostaglandin H2/thromboxane A2 receptor is responsible for the actions of 14, 15-cis- episulfide-eicosatrienoic acid. These properties distinguish 14, 15-cis- episulfide-eicosatrienoic acid from other antiaggregatory substances.

Volume 39, Issue 2, pp. 114-119, 02/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics