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Am J Physiol Renal Physiol 270: F61-F68, 1996;
0363-6127/96 $5.00
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AJP - Renal Physiology, Vol 270, Issue 1 61-F68, Copyright © 1996 by American Physiological Society

ARTICLES

Indirect coupling of urate and p-aminohippurate transport to sodium in human brush-border membrane vesicles

F. Roch-Ramel, B. Guisan and L. Schild
Institut de Pharmacologie et Toxicologie de l'Universite, Lausanne, Switzerland. francoise-roch-ramel@ipharm.unil.ch

[14C]urate and p-[14C]aminohippurate (PAH) uptake by human brush-border membrane vesicles (BBMV) were measured in the presence of an inwardly oriented sodium gradient. No direct sodium cotransport was observed. Indirect [14C]urate coupling to sodium transport was demonstrated by cis-stimulation of [14C]urate with nicotinate or pyrazinoate (PZA) in the extravesicular medium but not by adding lactate, alpha-ketoglutarate, or beta-hydroxybutyrate. Indirect sodium coupling of [14C]PAH uptake was observed only when alpha-ketoglutarate was added to the extravesicular medium, a mechanism similar to that of basolateral membranes. The ability for PZA (and nicotinate) to cis-stimulate urate uptake was correlated with a high apparent affinity for the urate/anion exchanger. In urate-loaded vesicles, for identical medium concentrations, [14C]PZA uptake via the urateanion exchanger was 10 times higher than [14C]lactate uptake. Such high PZA affinity for the urate exchanger, working in parallel with PZA sodium cotransport can account for the stimulation of urate reabsorption by PZA in vivo.


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