title: Antagonistic actions of S-145 on vascular and platelet thromboxane A2 receptors.
abstract: We studied the actions of a potent thromboxane A2/prostaglandin in H2 (TP) receptor antagonist, (+/-)-(5Z)-7-[3-endo-[(phenylsulfonyl)amino]bicyclo [2.2.1]hept-2-exo-yl]heptenoic acid (S-145) on vascular and platelet receptors in the pig. S-145 showed almost the same affinity for both receptors in ligand binding studies with [3H]U46619 or [3H]SQ29, 548. The binding affinity of S-145 was 5-8 times higher than that of SQ29,548, a well-characterized TP receptor antagonist. However, S-145 inhibited U46619-induced contractions of pig coronary arteries with an IC50 value 52.5 times lower than that of SQ29,548, and was approximately equipotent with SQ29,548 in inhibiting U46619-induced secondary aggregation of pig platelets. Detailed kinetic studies on [3H]S-145 binding revealed that the apparent discrepancy between the pharmacological potency of S-145 in platelet and vascular systems was not due to tissue selectivity, but its small association constants for both receptors.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Mihara
authors.forename: S
authors.initials: S
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Ide
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000378:metabolism*; D017482:Receptors, Thromboxane; D013552:Swine; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C056566:S 145; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548