Organic acid secretory pathway and urinary excretion of prostaglandin E in the dog.
Urinary prostaglandin E (PGE) has been utilized as an index of renal PGE production. Recent studies, however, have suggested that the organic acid secretory pathway is a major determinant of endogenous UPGEV (urinary excretion of PGE). The following experiments were designed to quantitatively test this latter view. In clearance studies the administration of para-aminohippurate (PAH) or probenecid (25 mg/kg) failed to alter endogenous UPGEV although PAH clearance fell with probenecid. Comparison of the excretion patterns of exogenously administered [3H]PGE and [14C]inulin after intra-arterial injection into the dog renal artery (Chinard technique) demonstrated both glomerular filtration and secretion of [3H]PGE. Blockade of the organic acid pathway by probenecid (25 mg/kg) abolished [3H]PGE secretion. Indomethacin (1 mg/kg) did not alter the secretion pattern of [3H]PGE, but decreased endogenous UPGEV by over 80%. Because this low dose of indomethacin did not decrease [3H]PGE secretion, it probably decreased endogenous UPGEV by inhibiting synthesis. Thus, these tracer studies do indeed confirm the suggestion that PGE may be excreted by the organic acid pathway. However, the failure of total endogenous UPGEV to fall after blockade of the organic acid pathway would suggest that the component of UPGEV due to this mechanism is quantitatively insignificant.
D000818:Animals; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011339:Probenecid / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism* / Q000652:urine; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D011458:Prostaglandins E; D011339:Probenecid; D007213:Indomethacin; D010130:p-Aminohippuric Acid