Substrate and inhibitor specificity of the lactate carrier of human neutrophils.
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.
Simchowitz
L
L
Department of Medicine, Veterans Affairs Medical Center, St. Louis, Missouri.
Vogt
S K
SK
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
D000085:Acetates; D000838:Anions; D002352:Carrier Proteins; D002934:Cinnamates; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D011422:Propionates; D013438:Sulfhydryl Compounds; D019344:Lactic Acid