Prostaglandin synthetase systems in rat and rabbit renal medulla and inhibition by non-steroidal anti-inflammatory drugs.
The properties of prostaglandin synthetase systems (PSSs) in the renal medulla of the rat and rabbit, and inhibition by ketoprofen, indomethacin, ibuprofen, phenylbutazone and aspirin were investigated in relation to their anti-inflammatory, analgesic, antipyretic and ulcerogenic activities. Rat and rabbit PSSs produced prostaglandin (PG)E and PGF from arachidonic and dihomo-gamma-linolenic acids and had an optimal pH of 8.5 and 7.5 for PGE formation, respectively. Only a slight loss of activity occurred with lyophilization. In the rat PSS, all drugs tested were inhibitory in the order of ketoprofen, ibuprofen, indomethacin and aspirin, respectively. In the rabbit PSS, the same potency relationship was also found. Drug sensitivity of the rat PSS was remarkably lower than that of the rabbit PSS. Significant correlations were noted between the inhibitory potencies of the drugs against both PSSs and other in vivo pharmacological activities within the same species.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007660:Ketoprofen / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D007679:Kidney Medulla / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010653:Phenylbutazone / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D011460:Prostaglandins F; D007660:Ketoprofen; D010653:Phenylbutazone; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin