title: Substrate and inhibitor specificity of the lactate carrier of human neutrophils.
abstract: The substrate and inhibitor specificity of the lactic acid (Lac) transport system of human neutrophils was investigated. The ability of a variety of compounds to inhibit the influx of [14C]lactate, presumably reflecting competition by substrate analogues for binding at the external translocation site, was taken as an index of affinity for the Lac carrier. pH-state techniques were utilized to assess transportability. Results indicate a relatively low order of selectivity, the neutrophil H+(+)lactate- cotransport system demonstrating a broad acceptance of short-chain unsubstituted and substituted alkyl monocarboxylates as well as aromatic monocarboxylates. There was a slight preference for oxo, Cl, and OH substituents over other groups at the two-position of short chain alkyl fatty acids: all were readily transported across the plasma membrane at rates approaching that of L-lactate itself. Aromatic acids were not transported inward by the carrier although these compounds did permeate via simple nonionic diffusion. The neutrophil Lac carrier can be blocked by a number of cyanocinnamate derivatives, the classical inhibitors of monocarboxylate transport in mitochondria, and by dithiol compounds and sulfhydryl-reactive agents. This constellation of biochemical properties is similar to the features that characterize other well described H+(+)lactate- cotransport systems in red blood cells, Ehrlich ascites tumor cells, hepatocytes, and cardiac sarcolemmal vesicles, although significant differences exist when comparisons are made to the Na(+)-dependent lactate transporter of the kidney proximal tubule.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, St. Louis, Missouri.
authors.forename: L
authors.initials: L
authors.lastname: Simchowitz
authors.forename: S K
authors.initials: SK
authors.lastname: Vogt
mesh_terms: D000085:Acetates / Q000378:metabolism; D000838:Anions / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000097:blood*; D002934:Cinnamates / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology
chemical_list: D000085:Acetates; D000838:Anions; D002352:Carrier Proteins; D002934:Cinnamates; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D011422:Propionates; D013438:Sulfhydryl Compounds; D019344:Lactic Acid