Cellular Activation of Thromboxane Receptors

Thromboxane A2 is an abundant and potent product of arachidonic acid metabolism in human platelets. Its clinical importance is highlighted by the efficacy of aspirin, which, due to its irreversible inhibition of the enzyme PGG/H synthase, selects the anucleate platelet as a particular target for extended duration of action. A single thromboxane receptor gene has been identified by southern blot; sequence polymorphism in the gene sequence has been identified. The recombinant receptor is also subject to posttranslational modifications, which may modify its affinity for natural ligands. Pharmacological studies have suggested some heterogeneity among thromboxane receptors. These observations have been rendered more interesting by the discovery of an F prostaglandin isomer, 8-epi-PGF2 alpha, which exerts its biological effects through a thromboxane (or closely related) receptor. This isomer can be generated in a free radical-catalyzed or cyclooxygenase-dependent manner.