engleski

Identification of a New Urate and High Affinity Nicotinate Transporter, hOAT10 (SLC22A13)

The orphan transporter hORCTL3 (human organic cation transporter like 3 ; SLC22A13) is highly expressed in kidneys and to a weaker extent in brain, heart, and intestine. hORCTL3-expressing Xenopus laevis oocytes showed uptake of [3H]nicotinate, [3H]p-aminohippurate, and [14C]urate. Hence, hORCTL3 is an organic anion transporter, and we renamed it hOAT10. [3H]Nicotinate transport by hOAT10 into X. laevis oocytes and into Caco-2 cells was saturable with Michaelis constants (Km) of 22 and 44 µ ; M, respectively, suggesting that hOAT10 may be the molecular equivalent of the postulated high affinity nicotinate transporter in kidneys and intestine. The pH dependence of hOAT10 suggests p-aminohippurate– /OH– , urate– /OH– , and nicotinate– /OH– exchange as possible transport modes. Urate inhibited [3H]nicotinate transport by hOAT10 with an IC50 value of 759 µ ; M, assuming that hOAT10 represents a low affinity urate transporter. hOAT10-mediated [14C]urate uptake was elevated by an exchange with L -lactate, pyrazinoate, and nicotinate. Surprisingly, we have detected urate– /glutathione exchange by hOAT10, consistent with an involvement of hOAT10 in the renal glutathione cycle. Uricosurics, diuretics, and cyclosporine A showed substantial interactions with hOAT10, of which cyclosporine A enhanced [14C]urate uptake, providing the first molecular evidence for cyclosporine A-induced hyperuricemia.

human kidney; organic anions; transport

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