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Received for publication April 10, 2006.
Revised May 16, 2006.
Accepted for publication May 16, 2006.
Intoxication with 
-hydroxybutyrate (GHB) is associated with coma, seizure and death; treatment of overdoses is symptomatic. Previous studies in our laboratory have demonstrated that L-lactate and pyruvate treatment can increase the renal clearance of GHB and increase its elimination in rats, suggesting that GHB may undergo renal reabsorption mediated by monocarboxylic acid transporters (MCT). The goals of this study were to (1) characterize the renal transport of GHB in rats and (2) determine the role of MCT in its renal transport. Brush-border membrane (BBM) and basolateral membrane (BLM) vesicles were isolated from rat kidney cortex and the uptake of L-lactate and GHB were characterized. L-lactate and GHB undergo both pH-dependent and sodium-dependent transport in BBM vesicles and pH-dependent transport in BLM vesicles. A simple Michaelis-Menten equation best described the pH-dependent uptake of GHB in BBM (Km of 8.0±1.8mM; Vmax of 838±45pmol/mg/sec) and in BLM vesicles (Km of 10.5±2.6mM; Vmax of 806±253pmol/mg/sec). mRNA of MCT1 and MCT2 was determined in rat kidney cortex using RT-PCR; using Western blot, the protein expression of MCT1 was present mainly in BLM vesicles, with weak expression in BBM vesicles, while that of MCT2 was exclusively in BLM vesicles. Studies with rat MCT1 gene-transfected MDA-MB231 cells, demonstrated that GHB was a substrate of MCT1. The data suggest that rat MCT1 may represent an important transporter for GHB in renal tubule cells. This investigation provides evidence for the importance of MCTs in the reabsorption of the monocarboxylic acids L-lactate and GHB in the kidney.
Key words:
MCT1, gamma-hydroxybutyrate, kidney, monocarboxylate, renal clearance, transport
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