Uric acid transport in rat renal basolateral membrane vesicles

Abstract

Pathways for urate transport across the basolateral membrane of rat proximal tubule cells were investigated using membrane vesicles isolated from rat renal cortex. The presence of an anion exchange mechanism(s) operative in the mode of α-ketoglutarate/urate; Cl −/urate and OH −(HCO 3 −)/urate as well as a mediated conductive mechanism was assessed from tracer flux measurements. In the presence of an inwardly directed Na + gradient an α-ketoglutarate dependent concentrative accumulation of PAH but not urate was observed suggesting an absence of the mediated exchange of α-ketoglutarate for urate. The imposition of an outwardly directed Cl − gradient stimulated urate uptake in the absence but not the presence of conditions designed to minimize membrane potential development suggesting an indirect electrostatic coupling of urate uptake to a Cl − gradient-induced diffusion potential. Conditions favoring the development of an inside-positive K + diffusion potential was observed to induce an inhibitor-sensitive, concentrative accumulation of urate in the absence of Cl −. The stimulation of urate uptake measured in the presence of an inside-alkaline pH gradient was not sufficient magnitude to suggest the apparent conductive urate uptake was secondary to a membrane voltage induced, inside alkaline pH gradient and the operation of an OH −(HCO 3 −)/urate exchanger. The evidence obtained from the present investigation suggests rat basolateral membrane urate transport occurs by a mediated, conductive mechanism and is not coupled to Cl −, α-ketoglutarate or HCO 3 −. This finding, when considered together with existing evidence supporting the presence of transport pathways mediating the active uptake of urate across the brush-border membrane, suggests the transtubular reabsorptive flux of urate in rat proximal tubules occurs by active uptake at the apical membrane and passive efflux at the basolateral membrane.