The goal of the proposed research is to extend our understanding of the renal tubular excretory transport of organic compounds with particular reference to the role of renal tubular synthesis of uric acid (urate) in the chicken, rat, dog and man. The relations between renal urate synthesis and plasma concentrations of hypoxanthine and xanthine will be studied. The role of renal secretory and reabsorptive mechanisms for urate in gout due to lead intoxication will also be studied in an attempt to localize a possible transport defect in saturine gout. In addition, the effects of drugs on peritubular and luminal excretory transport of uric acid as well as on reabsorption of uric acid will be determined by experimentally differentiating between: (a) the renal excretory transport of urate formed during the transfer of a precursor across the renal cell and, (b) the renal excretory transport of non-renal or exogenouse urate. We will attempt to localize the site of action of drugs such as thiazides, ethacrynic acid, furosemide, MK473, pyrazinoic acid and probenecid which alter the excretion of urate in man. BIBLIOGRAPHIC REFERENCES: Shideman, J. R., Zmuda, M. J. and Quebbemann, A. J.: The effects of ethacrynic acid (ECA), furosemide (F), and pyrazinoate(PA) on the renal tubular excretion of 14C-urate (UA) in the chicken: Evidence for urate reabsorption. American Society for pharmacology and Experimental Therapeutics, Fall Meeting, 1975 (Davis, Calif.), The Pharmacologist 17:252, 1976. Chin, T.Y. and Quebbemann, A.J.: Effects of hypoxanthine ad furosemide on renal excretion of urate synthesized in the chicken kidney. American Society for Pharmacology and Experimental Therapeutics, Fall Meeting, 1976 (New Orleans), The Pharmacologist 18:150, 1976.