Pharmacologic Characterization of Human and Canine Thromboxane A2/prostaglandin H2 Receptors in Platelets and Blood Vessels: Evidence for Different Receptors

The present study was undertaken to characterize thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors in platelets and blood vessels. Both human and canine platelet aggregation and saphenous vein contractions were induced by the stable TXA2/PGH2 mimetics (15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z, 13E-dienoic acid (U46619) and 9,11-epithio-11,12-methano-TXA2 (ONO-11113). ONO-11113 was a more potent agonist than U46619 in the human saphenous vein but less potent in the platelet. These agonists were equipotent in the canine platelet but ONO-11113 was more potent in the saphenous vein. Platelet aggregation and saphenous vein contraction induced by U46619 were blocked in a dose-dependent manner by the TXA2/PGH2 receptor agonists 9,11-dimethylmethano-11,12-methano-16-phenyl-13,14-dehydro-13-aza- 15 alpha beta-omega-tetranor-TXA2 (ONO-11120), 9,11-dimethylmethano-11,12-methano-16-(4-hydroxyphenyl)-13,14-d ihy dro-13-aza-15 alpha beta-omega-tetranor-TXA2 (PTA-OH), 9,11-dimethylmethano-11,12-methano-16-(4-methoxyphenyl)-13,14-d ihy dro-13-aza-15 alpha beta-omega-tetranor-TXA2 (PTA-OM), 9,11-dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl-13,1 4-dihydro-13- aza-15 alpha beta-omega-tetranor-TXA2 (I-PTA-OH) and 9,11-dimethylmethano-11,12-methano-15-phenyl-13,14-dihydro-13-aza- 15 alpha beta-omega-pentanor-TXA2 [PTA-(omega-1)].(ABSTRACT TRUNCATED AT 250 WORDS)