Inhibition of urate excretion by pyrazinoate: a micropuncture study.
Anesthetized monkeys (Cebus albifrons) undergoing moderate mannitol diuresis were treated with infusions containing lithium urate to elevate the urate concentration in plasma to 45-68 mug/ml and containing the uricosuric drug, 2-nitroprobenecid, to enhance the renal clearance or urate. The urate/inulin clearance ratio was 0.55 +/- 0.03. When pyrazinoate was added to the infusion the clearance ratio fell to 0.26 +/- 0.02. Analysis of free-flow micropuncture samples revealed a major effect of pyrazinoate in the proximal tubule, although an additional, smaller action in the distal tubule could not be definitely excluded. When droplets containing [14C]urate and [3H]inulin were streaked on the surface of the left kidney more urate than inulin appeared in the urine from that kidney (but not the other) within the first 3 min after application. This "excess" excretion of urate could be largely eliminated by pretreatment with pyrazinoate. The results suggest that pyrazinoate inhibits secretion of urate in the proximal tubule.
D000818:Animals; D002250:Carbon Radioisotopes; D005260:Female; D000882:Haplorhini; D007263:Infusions, Parenteral; D007444:Inulin; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D011339:Probenecid / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D014527:Uric Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine
D002250:Carbon Radioisotopes; D011719:Pyrazines; D014527:Uric Acid; D008353:Mannitol; D007444:Inulin; D011339:Probenecid