Comparative diuretic, saluretic, kaliuretic, and prostaglandin synthetase inhibitory activities of a competitive inhibitor of prostaglandin synthetase and spironolactone.
A newly described in vivo and in vitro competitive inhibitor of prostaglandin synthetase, 2-methyl, 8-cis, 12-trans, 14-cis, eicosatrienoic acid, a functional and structural analog of the endogenous substrates of prostaglandin E biosynthesis, as well as an analog of a putative intermediate in PGE1 biosynthesis, was shown to increase long-term urine excretion, and decrease long-term prostaglandin metabolite excretion in a linear dose-related manner. The correlation of both responses with dose were large (0.94, and 0.91 respectively), and nearly identical, within the limits of experimental error. In parallel studies, similar properties and nearly identical correlation coefficients were demonstrated for spironolactone, a known diuretic, suggesting that both drugs may be acting on mechanisms which may be closely associated and which may be involved in regulation of water and salt.
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000652:urine*; D011458:Prostaglandins E / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine*; D013148:Spironolactone / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D011458:Prostaglandins E; D013148:Spironolactone; C045515:2-methyl-8,12,14-eicosatrienoic acid; D012964:Sodium; D015126:8,11,14-Eicosatrienoic Acid; D011188:Potassium