Urate transport in brush-border membrane of human kidney.
Mechanisms of urate transport were investigated in human renal brush-border membrane vesicles. The imposition of an outwardly directed Cl- gradient, in voltage-clamp and pH-clamp conditions, stimulated [14C]urate uptake. Organic anions, including pyrazinoate (PZA), probenecid, lactate, ketone bodies, succinate, and alpha-ketoglutarate in their monovalent forms, cis-inhibited [14C]urate uptake. The affinity order was PZA > urate > probenecid > other anions. Vesicle preloading with these anions trans-stimulated urate uptake. These observations demonstrate the presence of a urate/anion exchanger. p-Aminohippurate and OH- were not substrates for this exchanger. In the presence of an inwardly directed K+ gradient and valinomycin (intravesicular positive potential) [14C]urate uptake was stimulated. Voltage-sensitive [14C]urate uptake was cis-inhibited by organic anions in the following affinity order: urate > probenecid > PZA. The differences in affinity orders for the urate exchanger and the urate voltage-sensitive transport suggest different pathways for apical transport. The anion exchanger might be the main mechanism involved in urate tubular reabsorption in humans.
Roch-Ramel
F
F
Institut de Pharmacologie et Toxicologie, Université, Lausanne, Switzerland.
Werner
D
D
Guisan
B
B
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000494:pharmacology; D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D002250:Carbon Radioisotopes; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000601:surgery; D007700:Kinetics; D007773:Lactates / Q000494:pharmacology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D011339:Probenecid / Q000494:pharmacology; D014527:Uric Acid / Q000378:metabolism*; D014634:Valinomycin / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D000090:Acetoacetates; D002250:Carbon Radioisotopes; D006885:Hydroxybutyrates; D007773:Lactates; D014634:Valinomycin; D014527:Uric Acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C016635:acetoacetic acid; D011339:Probenecid; D020155:3-Hydroxybutyric Acid; D010130:p-Aminohippuric Acid