Evidence for homogeneity of thromboxane A2 receptor using structurally different antagonists.
Nine structurally dissimilar thromboxane antagonists (SQ 29548, ICI 185282, AH 23848, BM 13505 (Daltroban), BM 13177 (Sulotroban), SK&F 88046, L-636499, L-640035 and a Bayer compound SK&F 47821) were studied for activity as thromboxane A2 receptor antagonists. The assays used were inhibition of responses induced by the thromboxane mimetic, U46619, on human washed platelet aggregation, rabbit platelet aggregation, rabbit aortic strip contraction, anaesthetised guinea-pig bronchoconstriction, and a radio-labelled ligand (125I-PTA-OH) binding assay as a measure of affinity for the human platelet receptor. The results of the present study, with activities spanning at least four orders of magnitude along with statistically significant correlations (at least P less than 0.01), strongly suggests that between assays, antagonists and species a homogenous population of thromboxane A2 receptors exists. This finding is in contrast to those of a close series of 13-azapinane antagonists studied by other workers which have suggested receptor heterogeneity.
Swayne
G T
GT
Department of Pharmacology, Smith Kline & French Research Limited, Hertfordshire, U.K.
Maguire
J
J
Dolan
J
J
Raval
P
P
Dane
G
G
Greener
M
M
Owen
D A
DA
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes