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Articles in PresS, published online ahead of print June 13, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00380.2001
Submitted on August 7, 2001
Accepted on June 6, 2002
1 Pharmacology, State University of New York Upstate Medical University, Syracuse, NY, USA
* To whom correspondence should be addressed. E-mail: Grassls{at}upstate.edu.
Membrane transport pathways mediating transcellular secretion of urate across the proximal tubule were investigated in brush border membrane vesicles isolated from avian kidney. An inside-positive K diffusion potential induced a conductive uptake of urate to levels exceeding equilibrium. Protonophore-induced dissipation of membrane potential significantly reduced voltage-driven urate uptake. Conductive uptake of urate was inhibitor-sensitive, substrate-specific and a saturable function of urate concentration. Urate uptake was trans-stimulated by urate and cis-inhibited by p-aminohippurate (PAH). Conductive uptake of PAH was cis-inhibited by urate. Urate uptake was unaffected by an outward
-ketoglutarate gradient. In the absence of a membrane potential, urate uptake was similar in the presence and absence of an imposed inside-alkaline pH gradient or an outward Cl gradient. These observations suggest a uniporter-mediated facilitated diffusion of urate as a pathway for passive efflux across the brush border membrane of urate secreting proximal tubule cells.
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