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Formation of 6‐keto prostaglandin E 1 in mammalian kidneys
Author(s) -
Griffiths R.J.,
Moore P.K.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb10507.x
Subject(s) - kidney , metabolite , prostaglandin e , endocrinology , medicine , guinea pig , prostaglandin , nad+ kinase , prostacyclin , chemistry , carbenoxolone , biology , biochemistry , intracellular , enzyme , gap junction
1 The metabolism of prostacyclin (PGI 2 ) and 6‐keto prostaglandin F 1α (6‐keto PGF 1α ) was studied in cell‐free homogenates of rat, rabbit and guinea‐pig kidney. 2 Rabbit kidney converted both PGI 2 and 6‐keto PGF 1α to a stable metabolite with chromatographic and biological activity identical to that of authentic 6‐keto PGE 1 . Activity was found in the kidney cortex but not medulla, was inhibited by NAD + or NADP + (5 m M ) and showed an optimum temperature requirement of 37°C. 3 Guinea‐pig kidney converted PGI 2 but not 6‐keto PGF 1α to a labile, biologically active metabolite which was not 6‐keto PGE 1 . 4 No conversion of prostacyclin or 6‐keto PGF 1α to biologically active metabolites occurred in cell‐free homogenates of rat kidney, liver and colon or guinea‐pig liver and colon. 5 6‐keto PGE 1 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. 6 Rutin (50 μ M ) potently inhibited synthesis of 6‐keto PGE 1 from added PGI 2 by rabbit kidney cortex. This reaction was potentiated by a similar concentration of sulphasalazine, carbenoxolone, imidazole, papaverine or indomethacin. 7 The relevance of these findings for the possible physiological and pathological roles of 6‐keto PGE 1 in the kidney is discussed.