6-Keto-Prostaglandin E1: Its Formation by Platelets from Prostacyclin and Resistance to Pulmonary Degradation

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Abstract
6-Keto-prostaglandin E (6-keto-PGE1) is a novel biologically active product of the metabolism of prostacyclin in liver and platelets. Further evidence for this bioconversion was obtained in stirred suspensions of platelet rich plasma (PRP) and resuspended platelets (RSP) by sampling and simultaneous assay on a superfusion cascade (rabbit celiac artery, rat stomach fundus strip) and on human platelet aggregation. Incubation of prostacyclin in saline led to rapid loss of bioactivity (t1/2 [half-life] 3.2 min); its stability was prolonged in platelet poor plasma (t1/2 25.1 min). However, in PRP and RSP a more spasmogenic product was generated transiently. Apparently 6-Keto-PGE1, was 3.0 and 2.5 times more potent on the 2 bioassay tissues, respectively, but approximately 3 times less so as inhibitor of platelet aggregation. Apparently 6-Keto-PGE1 is not extensively metabolized in the isolated perfused rat lung (20.4 or 4.2%, depending on protocol), compared with PGE1 (84.3 or 78.5%), and is a much poorer substrate for the principal prostaglandin metabolizing enzyme, prostaglandin 15-hydroxydehydrogenase. 6-Keto-PGE1 apparently is a biologically active but pulmonary-resistant product of prostacyclin metabolism but does not resolve the claim that it might have physiological relevance.