Characterization of beta-hydroxybutyrate transport in rat erythrocytes and thymocytes.
A method was developed for study of beta-hydroxybutyrate transport in erythrocytes and thymocytes. Critical to the method was a centrifugal separation of cells from medium which took advantage of beta-hydroxybutyrate transport's temperature dependence and inhibition by phloretin and methylisobutylxanthine, all of which are demonstrated in this work. These properies suggested mediated transport, as did saturation kinetics and inhibition by several agents including pyruvate and alpha-cyanocinnamate. Most conclusive in this regard was a 2-fold preference for D- over L-beta-hydroxybutyrate. Entry was not Na+ dependent. It was stimulated by substitution of SO2-4 for most of the Cl-. The equilibrium beta-hydroxybutyrate space was much higher than the Cl- space of thymocytes, suggesting that beta-hydroxybutyrate entry is not associated with net inward negative current and is not coupled to outward Cl- or inward K+ movement (assuming that K+ is at elecrochemical equilibrium). Coupling to H+ entry or OH- exit is compatible with the result. These findings are consistent with beta-hydroxybutyrate entry by the carboxylate transport site which has been studied extensively with pyruvate and lactate as permeants. The Cl-/HCO-3 exchange carrier did not appear to contribute significantly to beta-hydroxybutyrate transport.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002254:Carbonates / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000097:blood*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism*; D013696:Temperature
D002254:Carbonates; D002712:Chlorides; D006885:Hydroxybutyrates; D012964:Sodium; D011188:Potassium