Formation of 6‐keto prostaglandin E1 in mammalian kidneys
- 1 May 1983
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 79 (1), 149-155
- https://doi.org/10.1111/j.1476-5381.1983.tb10507.x
Abstract
1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha 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 degrees C. 3 Guinea-pig kidney converted PGI2 but not 6-keto PGF1 alpha to a labile, biologically active metabolite which was not 6-keto pge1. 4 No conversion of prostacyclin or 6-keto PGF1 alpha to biologically active metabolites occurred in cell-free homogenates of rat kidney, liver and colon or guinea-pig liver and colon. 5 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. 6 Rutin (50 microM) 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. 7 The relevance of these findings for the possible physiological and pathological roles of 6-keto PGE1 in the kidney is discussed.Keywords
This publication has 21 references indexed in Scilit:
- Release of biologically active substances from non-aggregating human plateletsEuropean Journal of Pharmacology, 1982
- A radioimmunoassay for 6-ketoprostaglandin E1Prostaglandins, Leukotrienes and Medicine, 1982
- Measurement of 13,14-dihydro-6,15-dioxo PGF1α by radioimmunoassay: Application to the study of prostacyclin metabolismProgress in Lipid Research, 1981
- Formation and elimination of prostacyclin metabolites in the cat in vivo as determined by radioimmunoassay of unextracted plasmaEuropean Journal of Pharmacology, 1981
- 6-Keto-PGE1 exhibits more potent bronchodilatory activity in the cat than its precursor, PGI2Prostaglandins, 1981
- 6-Keto-prostaglandin E1 is not equipotent to prostacyclin (PGI2) as an antiaggregatory agentProstaglandins, 1980
- Hepatic metabolism of prostacyclin (PGI2) in the rabbit: Formation of a potent novel inhibitor of platelet aggregationBiochemical and Biophysical Research Communications, 1980
- Hypotensive and renovascular actions of 6-keto-prostaglandin E1, a metabolite of prostacyclinEuropean Journal of Pharmacology, 1979
- Metabolism of prostacyclin. III. Urinary metabolite profile of 6-keto PGF1α in ratProstaglandins, 1979
- Prostaglandin metabolism in rabbit kidneyBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1978