Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
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Am J Physiol Cell Physiol (June 13, 2002). doi:10.1152/ajpcell.00379.2001
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Articles in PresS, published online ahead of print June 13, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00379.2001
Submitted on August 7, 2001
Accepted on June 6, 2002

Urate /{alpha}- Ketoglutarate Exchange in Avian Basolateral Membrane Vesicles

Steven M. Grassl1*

1 Pharmacology, State University of New York Upstate Medical University, Syracuse, New York, USA

* To whom correspondence should be addressed. E-mail: grassls{at}upstate.edu.

Membrane transport pathways for transcellular secretion of urate across the proximal tubule were investigated in avian kidney. The presence of coupled urate/{alpha}-ketoglutarate exchange was investigated in basolateral membrane vesicles by [14C]urate and [3H]{alpha}-ketoglutarate flux measurements. An inward Na gradient induced accumulation of {alpha}-ketoglutarate of sufficient magnitude to suggest a Na-dicarboxylate cotransporter. An inward Na gradient also induced concentrative accumulation of urate in the presence of {alpha}-ketoglutarate but not in its absence, suggesting urate/{alpha}-ketoglutarate exchange. {alpha}-Ketoglutarate-dependent stimulation of urate uptake was not observed in brush border membrane vesicles. An outward urate gradient induced concentrative accumulation of {alpha}-ketoglutarate. {alpha}-Ketoglutarate-coupled urate uptake was specific for {alpha}-ketoglutarate, Cl-dependent, and insensitive to membrane potential. {alpha}-ketoglutarate-coupled urate uptake was inhibited by increasing PAH concentrations and {alpha}-ketoglutarate-coupled PAH uptake was observed. {alpha}-ketoglutarate-coupled PAH uptake was inhibited by increasing urate concentrations and an outward urate gradient induced concentrative accumulation of PAH. These results suggest a Cl-dependent, {alpha}-ketoglutarate-coupled anion exchange mechanism as a pathway for active urate uptake across the basolateral membrane of urate secreting proximal tubule cells.




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