Formation of 6‐keto prostaglandin E1 in mammalian kidneys

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Abstract
The metabolism of prostacyclin (PGI2) and 6‐keto prostaglandin F1α (6‐keto PGF1α) was studied in cell‐free homogenates of rat, rabbit and guinea‐pig kidney. Rabbit kidney converted both PGI2 and 6‐keto PGF1α to a stable metabolite with chromatographic and biological activity identical to that of authentic 6‐keto PGE1. Activity was found in the kidney cortex but not medulla, was inhibited by NAD+ or NADP+ (5 mM) and showed an optimum temperature requirement of 37°C. Guinea‐pig kidney converted PGI2 but not 6‐keto PGF1α to a labile, biologically active metabolite which was not 6‐keto PGE1. No conversion of prostacyclin or 6‐keto PGF1α to biologically active metabolites occurred in cell‐free homogenates of rat kidney, liver and colon or guinea‐pig liver and colon. 6‐keto PGE1 rapidly lost spasmogenic activity on the rat stomach strip following incubation with rabbit or guinea‐pig kidney supernatant in the absence of added cofactors. No loss of activity occurred on incubation with rat kidney. Rutin (50 μM) potently inhibited synthesis of 6‐keto PGE1 from added PGI2 by rabbit kidney cortex. This reaction was potentiated by a similar concentration of sulphasalazine, carbenoxolone, imidazole, papaverine or indomethacin. The relevance of these findings for the possible physiological and pathological roles of 6‐keto PGE1 in the kidney is discussed.