Thromboxane A2 and prostaglandin endoperoxide receptors in platelets and vascular smooth muscle.
9,11-Dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl)-13, 14-dihydro-13-aza-15 alpha beta-omega-tetranor-TXA2 (I-PTA-OH), a recently synthesized thromboxane (TX) A2/prostaglandin (PG) H2 receptor antagonist, was shown to be a competitive antagonist of human platelet aggregation induced by the stable endoperoxide analog U46619. This antagonism was due to competitive blockade of the platelet TXA2/PGH2 receptor since I-PTA-OH did not antagonize the first phase of ADP-induced aggregation which is TXA2/PGH2 independent, nor did it inhibit TXA2 synthesis. In addition, analysis of dose-response curves to U46619 (0.1 to 40 microM) in the presence of increasing concentrations of I-PTA-OH (0.5 to 10 microM) showed that I-PTA-OH produced a parallel rightward shift of the dose-response curve. Further analysis of the data in the form of a Schild plot yielded a straight line with a slope (m = 1.03) not significantly different from -1. These results are consistent with the notion that I-PTA-OH acts as a competitive antagonist of the TXA2/PGH2 receptor.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001792:Blood Platelets / Q000032:analysis*; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000032:analysis*; D010974:Platelet Aggregation / Q000187:drug effects; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000032:analysis*; D011982:Receptors, Prostaglandin / Q000032:analysis* / Q000187:drug effects; D017482:Receptors, Thromboxane; D013329:Structure-Activity Relationship; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
D007457:Iodine Radioisotopes; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C046957:I-PTA-OH