Indirect coupling of urate and p-aminohippurate transport to sodium in human brush-border membrane vesicles.
[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.
Roch-Ramel
F
F
Institut de Pharmacologie et Toxicologie de l'Universite, Lausanne, Switzerland. francoise-roch-ramel@ipharm.unil.ch
Guisan
B
B
Schild
L
L
D000368:Aged; D001692:Biological Transport; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D008875:Middle Aged; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D019354:Sodium Lactate / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism*; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D014527:Uric Acid; D011718:Pyrazinamide; C005296:pyrazinoic acid; D012964:Sodium; D019354:Sodium Lactate; D010130:p-Aminohippuric Acid