Publications

• Urate and p-aminohippurate transport in rat renal basolateral vesicles.

  Kahn A.M., Shelat H., Weinman E.J.

  We examined the transport of urate in basolateral membrane vesicles from the rat kidney and determined the relationship between the transport of urate and p-aminohippurate (PAH). Urate was not converted to allantoin, and the uptake of urate represented transport into an osmotically active intraves ... >> More

  We examined the transport of urate in basolateral membrane vesicles from the rat kidney and determined the relationship between the transport of urate and p-aminohippurate (PAH). Urate was not converted to allantoin, and the uptake of urate represented transport into an osmotically active intravesicular space. The 10-s uptake of 53 microM [14C]urate in basolateral vesicles was inhibited 39 +/-6, 49 +/- 10, and 35 +/-3% by (in mM) external 2.4 probenecid, 2.4 DIDS, and 1.4 unlabeled urate, respectively. The 10-s uptake of 353 microM [14C]urate was trans-stimulated 82 +/-8% by preloading basolateral vesicles with 1.5 mM unlabeled urate. The uptake of urate was stimulated by an outwardly directed gradient for Cl-(Cl-in = 25 mM, Cl-out = 5 mM). This effect was not consequent to a more electropositive intravesicular space, as monitored by the voltage-sensitive sodium-L-malate cotransport system. The Cl-gradient-stimulated component of urate uptake in basolateral vesicles was not cis-inhibited by 4.8 mM PAH, whereas Cl gradient-stimulated urate uptake in brush border vesicles was cis-inhibited 43 +/-5% by PAH. In the absence of Cl-, 4.8 mM PAH did not cis-inhibit, and 5.4 mM PAH or 6.4 mM lactate did not trans-stimulate the uptake of urate in basolateral vesicles, contrasting with results obtained with brush border vesicles. The uptake of urate in basolateral vesicles was not stimulated by external Na+ relative to K+, Li+, or Cs+. In contrast, PAH uptake in basolateral vesicles was stimulated 87 +/- 9% by external Na+.(ABSTRACT TRUNCATED AT 250 WORDS) << Less

  Am J Physiol 249:F654-61(1985) [PubMed] [EuropePMC]

• Molecular identification of a renal urate anion exchanger that regulates blood urate levels.

  Enomoto A., Kimura H., Chairoungdua A., Shigeta Y., Jutabha P., Cha S.H., Hosoyamada M., Takeda M., Sekine T., Igarashi T., Matsuo H., Kikuchi Y., Oda T., Ichida K., Hosoya T., Shimokata K., Niwa T., Kanai Y., Endou H.

  Urate, a naturally occurring product of purine metabolism, is a scavenger of biological oxidants implicated in numerous disease processes, as demonstrated by its capacity of neuroprotection. It is present at higher levels in human blood (200 500 microM) than in other mammals, because humans have a ... >> More

  Urate, a naturally occurring product of purine metabolism, is a scavenger of biological oxidants implicated in numerous disease processes, as demonstrated by its capacity of neuroprotection. It is present at higher levels in human blood (200 500 microM) than in other mammals, because humans have an effective renal urate reabsorption system, despite their evolutionary loss of hepatic uricase by mutational silencing. The molecular basis for urate handling in the human kidney remains unclear because of difficulties in understanding diverse urate transport systems and species differences. Here we identify the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricosuric agents (which affect excretion of uric acid). Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12. Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution. << Less

  Nature 417:447-452(2002) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Urate transport in brush-border membrane of human kidney.

  Roch-Ramel F., Werner D., Guisan B.

  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 bodie ... >> More

  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. << Less

  Am J Physiol 266:F797-805(1994) [PubMed] [EuropePMC]