@article {Lamdmd.109.030775, author = {Wing Ki Lam and Melanie A. Felmlee and Marilyn E. Morris}, title = {Monocarboxylate Transporter (MCT)-mediated transport of γ-hydroxybutyric acid in human intestinal Caco-2 cells}, elocation-id = {dmd.109.030775}, year = {2009}, doi = {10.1124/dmd.109.030775}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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 {\textpm} 10.5 mM; Vmax, 17.3 {\textpm} 11.7 nmol/min/mg; P, 0.38 {\textpm} 0.15 μl/min/mg) and D-lactate (Km, 6.0 {\textpm} 2.9 mM; Vmax, 35.0 {\textpm} 18.4 nmol/min/mg; P, 1.3 {\textpm} 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}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/early/2009/12/01/dmd.109.030775}, eprint = {https://dmd.aspetjournals.org/content/early/2009/12/01/dmd.109.030775.full.pdf}, journal = {Drug Metabolism and Disposition} }