Binding of thromboxane A2/prostaglandin H2 agonists to human platelets.
The competition of [125I]-9, 11 dimethylmethano-11, 12 methano-16-(3-iodo-4-hydroxyphenyl)-13, 14-dihydro-13-aza 15 alpha beta-omega-tetranor-thromboxane A2 ([125I]-PTA-OH), a thromboxane A2/prostaglandin H2 receptor antagonist, with a series of thromboxane A2/prostaglandin H2 (TXA2/PGH2) mimetics for binding to the putative TXA2/PGH2 receptor in washed human platelets was studied. The rank order potency for the series of mimetics to compete with [125I]-PTA-OH for binding was compared with their rank order potency for induction of platelet aggregation. The rank order potency for the mimetics to compete with [125I]-PTA-OH for binding was ONO-11113 greater than SQ-26655 greater than U44069 greater than U46619 = 9, 11-azo PGH2 greater than MB28767. This rank order potency was highly correlated with their rank order potency for inducing platelet aggregation (r = 0.992). Changes in the intra or extracellular concentrations of Na+ did not have a significant effect on the competition between U46619 and [125I]-PTA-OH for binding to the putative receptor. In summary, it appears that these TXA2/PGH2 mimetics activate human platelets through the putative TXA2/PGH2 receptor.
D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D010974:Platelet Aggregation / Q000187:drug effects; D011449:Prostaglandin Endoperoxides / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000502:physiology*; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000378:metabolism; D012964:Sodium / Q000097:blood / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*
D007457:Iodine Radioisotopes; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D044262:Prostaglandin H2; D013928:Thromboxane A2; C046957:I-PTA-OH; D012964:Sodium