salicylates and Kidney-Neoplasms

Topics: Acetaminophen; Analgesics; Animals; Aspirin; Carcinoma, Transitional Cell; Female; Humans; Kidney Neoplasms; Kidney Papillary Necrosis; Male; Microsomes, Liver; Phenacetin; Rats; Salicylates; Spermatogenesis; Substance-Related Disorders

Inhibition of [14C]-urate uptake by uricosuric and antiuricosuric agents was investigated in human brush-border membrane vesicles, urate being transported either by anion exchange mechanisms or by voltage sensitive pathway. The IC50 for drugs on [14C]-urate uptake in vesicles loaded with 1 mM cold urate or with 5 mM lactate was, respectively: 0.7 and 0.3 microM for benzbromarone; 6 and 4 microM for salicylate; 133 and 13 microM for losartan; 520 and 190 microM for sulfinpyrazone and 807 and 150 microM, for probenecid. The IC50 ratio for [14C]-urate uptake in exchange for cold urate or for lactate varied from about 1 for salicylate to 10 for losartan, supporting the hypothesis that two distinct anion exchangers are involved in urate transport. Application of Hill equation revealed that urate/anion exchangers have more than one binding site, possibly two binding sites with high cooperativity, for benzbromarone and sulfinpyrazone, but only one for probenecid, salicylate and losartan. The uricosuric diuretic, tienilic acid was 10 to 50 times more potent than hydrochlorothiazide, chlorothiazide and furosemide, for inhibiting [14C]-urate uptake in exchange for cold urate. This higher potency is the reason of its uricosuric properties. All uricosuric agents, as well as the antiuricosuric agents, pyrazinoate and ethambutol, had a much lower potency for inhibiting [14C]-urate uptake through the voltage sensitive pathway (apical secretory step) than through the urate/anion exchangers. This suggests that antiuricosuria, induced by pyrazinoate and ethambutol, as well as by low concentrations of uricosuric agents, does not result from an inhibition of the apical voltage sensitive pathway.

Topics: Aged; Benzbromarone; Biological Transport; Biphenyl Compounds; Carbon Radioisotopes; Diuretics; Ethambutol; Humans; Imidazoles; Kidney Cortex; Kidney Neoplasms; Kinetics; Losartan; Microvilli; Middle Aged; Probenecid; Pyrazinamide; Salicylates; Salicylic Acid; Sulfinpyrazone; Tetrazoles; Ticrynafen; Uric Acid; Uricosuric Agents

Topics: Age Factors; Antipyrine; Caffeine; Female; Humans; Kidney Failure, Chronic; Kidney Neoplasms; Kidney Pelvis; Male; Papilloma; Phenacetin; Salicylates; Sex Factors; Substance-Related Disorders; Sweden; Time Factors

Topics: Acetaminophen; Antipyrine; Denmark; Humans; Kidney Diseases; Kidney Neoplasms; Kidney Papillary Necrosis; Legislation, Drug; Phenacetin; Pyelonephritis; Salicylates; Substance-Related Disorders; Sweden; Switzerland; Urinary Bladder Neoplasms