title: 14, 15-cis-episulfide-eicosatrienoic acid, an 'epoxygenase' eicosanoid analog, inhibits ionophore- but not thrombin-induced platelet aggregation.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: K
authors.initials: K
authors.lastname: Bernstrom
authors.forename: K
authors.initials: K
authors.lastname: Malcolm
authors.forename: J
authors.initials: J
authors.lastname: McGee
authors.forename: J
authors.initials: J
authors.lastname: Maclouf
authors.forename: S
authors.initials: S
authors.lastname: Levy-Toledano
authors.forename: J R
authors.initials: JR
authors.lastname: Falck
authors.forename: F A
authors.initials: FA
authors.lastname: Fitzpatrick
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology; D000001:Calcimycin / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D013917:Thrombin / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D010975:Platelet Aggregation Inhibitors; D000001:Calcimycin; D013929:Thromboxane B2; D003094:Collagen; C067407:14,15-episulfide eicosatrienoic acid; D000242:Cyclic AMP; D013917:Thrombin; D015126:8,11,14-Eicosatrienoic Acid; D002118:Calcium