9α,11β-Prostaglandin F2: A New Prostanoid, That Inhibits Platelet Aggregation and Constricts Blood Vessels
Nugteren and Hazelhof (1)were the first to report the formation of PGD2 from endoperoxides (PGG2 and PGH2). Subsequently, PGD2 was found to be one of the major products of arachidonic acid cascade in many tissue and cell types (2). Since then the transformation of PGH2 to PGD2 has been demonstrated in brain homogenates (3,4) and neuroblastoma cells (5). The enzyme PGD2 synthetase, which catalyzed the conversion of PGH2 to PGD2, has been purified to homogeneity and clearly distinguished from that of glutathione-S-transferase(6). It has been reported that PGD2 is released by platelets during aggregation (7) and was found to be a potent inhibitor of platelet aggregation, with a potency only less than that of prostacyclin (PGI2) and its stable biologically active metabolite, 6-keto-PGE1 (8,9). The metabolism of prostaglandin D2 in the monkey has been reported by Ellis et al. (10), who found that more than two-thirds of the PGD2 metabolites have the cyclopentane 1,3-diol ring structure (PGF2α). These workers postulated the existence of an enzyme 11-ketoreductase which may have converted the infused PGD2 to PGF2α before it was further degraded by 15-hydroxyprostaglandin dehydrogenase and β-oxidation.
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