Different pharmacologic activities for 13-azapinane thromboxane A2 analogs in platelets and blood vessels. 1988

D E Mais, and D DeHoll, and H Sightler, and P V Halushka
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.

A series of 16 13-azapinane thromboxane A2 analogs were synthesized and their pharmacological dissociation constants (Kd) determined for the thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor in both washed human platelets and canine saphenous veins. Twelve of the analogs were antagonists of both U46619-induced platelet aggregation and saphenous vein contraction. The rank order potencies of these analogs were significantly different in platelets compared to saphenous veins. Four of the derivatives were antagonists in the platelets but possessed agonist activity in the vessels. The potency of the analogs and the type of activity (agonist or antagonist) were found to be sensitive to the substitution pattern of the aromatic ring on the bottom side chain. These results further support the notion that platelet TXA2/PGH2 receptors are distinct from that of vascular receptors.

UI MeSH Term Description Entries
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D011982 Receptors, Prostaglandin Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors). Prostaglandin Receptors,Prostaglandin Receptor,Receptor, Prostaglandin,Receptors, Prostaglandins,Prostaglandins Receptors
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D001808 Blood Vessels Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins). Blood Vessel,Vessel, Blood,Vessels, Blood
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013928 Thromboxane A2 An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS). Rabbit Aorta Contracting Substance,A2, Thromboxane
D014661 Vasoconstriction The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE. Vasoconstrictions

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