title: Monocarboxylate transporter-mediated transport of gamma-hydroxybutyric acid in human intestinal Caco-2 cells.
abstract: The objectives of this study were to determine mRNA expression of monocarboxylate transporters (MCT) and to evaluate intestinal transport of the MCT substrates gamma-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 was best described by a Michaelis-Menten equation with passive diffusion (GHB: K(m) = 17.6 +/- 10.5 mM, V(max) = 17.3 +/- 11.7 nmol/min/mg, and P = 0.38 +/- 0.15 microl/min/mg; and d-lactate: K(m) = 6.0 +/- 2.9 mM, V(max) = 35.0 +/- 18.4 nmol/min/mg, and P = 1.3 +/- 0.6 microl/min/mg). The uptake of GHB and d-lactate was significantly decreased by the known MCT inhibitor alpha-cyano-4-hydroxycinnamate and the MCT substrates GHB and d-lactate but not by the organic cation tetraethylammonium chloride. 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 that in the basolateral to apical direction. These findings confirm the presence of MCT1-4 in Caco-2 cells and demonstrate GHB and d-lactate transport characteristics consistent with proton-dependent MCT-mediated transport.
authors: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, New York, USA.
authors: Wing Ki
authors: WK
authors: Lam
authors: Melanie A
authors: MA
authors: Felmlee
authors: Marilyn E
authors: ME
authors: Morris
mesh_terms: D018938:Caco-2 Cells; D016764:Cell Polarity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006885:Hydroxybutyrates / Q000378:metabolism* / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D049990:Membrane Transport Modulators / Q000494:pharmacology; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017711:Nonlinear Dynamics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium
chemical_list: D006885:Hydroxybutyrates; D049990:Membrane Transport Modulators; D027501:Monocarboxylic Acid Transporters; D020033:Protein Isoforms; D012333:RNA, Messenger; C111420:4-hydroxybutyric acid; D019344:Lactic Acid; D012964:Sodium