PT - JOURNAL ARTICLE AU - Wing Ki Lam AU - Melanie A. Felmlee AU - Marilyn E. Morris TI - Monocarboxylate Transporter (MCT)-mediated transport of γ-hydroxybutyric acid in human intestinal Caco-2 cells AID - 10.1124/dmd.109.030775 DP - 2009 Jan 01 TA - Drug Metabolism and Disposition PG - dmd.109.030775 4099 - http://dmd.aspetjournals.org/content/early/2009/12/01/dmd.109.030775.short 4100 - http://dmd.aspetjournals.org/content/early/2009/12/01/dmd.109.030775.full AB - The objectives of this study were to determine mRNA expression of MCT transporters, and to evaluate intestinal transport of the MCT substrates, γ-hydroxybutyrate (GHB) and D-lactate in human intestinal Caco-2 cells. The presence of mRNA for MCT1, 2, 3 and 4 was observed in Caco-2 cells. The uptake of both GHB and D-lactate in Caco-2 cells was demonstrated to be pH- and concentration-dependent, and sodium-independent. The uptake of GHB and D-lactate were described by a Michaelis-Menten equation with passive diffusion; GHB (Km, 17.6 ± 10.5 mM; Vmax, 17.3 ± 11.7 nmol/min/mg; P, 0.38 ± 0.15 μl/min/mg) and D-lactate (Km, 6.0 ± 2.9 mM; Vmax, 35.0 ± 18.4 nmol/min/mg; P, 1.3 ± 0.6 μl/min/mg). The uptake of GHB and D-lactate were significantly decreased by the known MCT inhibitor, α-cyano-4-hydroxycinnamate, and the MCT substrates GHB and D-lactate and but not by the organic cation TEA. Directional flux studies with both GHB and D-lactate suggested the involvement of carrier-mediated transport with the permeability in the apical to basolateral direction higher than the basolateral to apical direction. These findings confirm the presence of MCTs 1-4 in Caco-2 cells and demonstrate GHB and D-lactate transport characteristics consistent with proton-dependent MCT-mediated transport.The American Society for Pharmacology and Experimental Therapeutics