Different pharmacologic activities for 13-azapinane thromboxane A2 analogs in platelets and blood vessels.
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.
Mais
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DE
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.
DeHoll
D
D
Sightler
H
H
Halushka
P V
PV
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D001808:Blood Vessels / Q000502:physiology*; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D011982:Receptors, Prostaglandin / Q000502:physiology*; D017482:Receptors, Thromboxane; D013329:Structure-Activity Relationship; D013928:Thromboxane A2 / Q000031:analogs & derivatives*; D014661:Vasoconstriction / Q000187:drug effects
D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2