Summary
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-stat 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 ofl-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.
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Simchowitz, L., Vogt, S.K. Substrate and inhibitor specificity of the lactate carrier of human neutrophils. J. Membrain Biol. 131, 23–34 (1993). https://doi.org/10.1007/BF02258531
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DOI: https://doi.org/10.1007/BF02258531