title: Characterization of thromboxane A2/prostaglandin H2 receptors in porcine coronary artery--the inhibitory effect of a novel dibenzoxepin derivative, KW-3635.
abstract: We characterized the thromboxane A2/prostaglandin H2 receptors in porcine coronary artery. The binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to coronary arterial membranes was saturable and displaceable. Scatchard analysis of equilibrium binding showed a single class of high affinity binding sites with a dissociation constant of 18.5 +/- 1.0 nM and the maximum binding of 80.7 +/- 5.2 fmol/mg protein. [3H]SQ 29,548 binding was concentration-dependently inhibited by thromboxane A2 antagonists such as SQ 29,548, BM13505 and BM13177 or the thromboxane A2 agonists such as U46619 and U44069. KW-3635, a novel dibenzoxepin derivative, concentration-dependently inhibited the [3H]SQ 29,548 binding to thromboxane A2/prostaglandin H2 receptors in coronary artery with an inhibition constant of 6.0 +/- 0.69 nM (mean +/- S.E.M.).
authors.affiliation: Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Miki
authors.forename: A
authors.initials: A
authors.lastname: Ishii
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001584:Benzoxepins / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003331:Coronary Vessels / Q000187:drug effects*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D011463:Prostaglandins H; D011869:Radioligand Assay; D011982:Receptors, Prostaglandin / Q000737:chemistry* / Q000187:drug effects; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013552:Swine; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
chemical_list: D001562:Benzimidazoles; D001584:Benzoxepins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2; C045749:SQ 29548; C065729:KW 3635