title: Cytosolic pH regulation in mouse macrophages. Proton extrusion by plasma-membrane-localized H(+)-ATPase.
abstract: Recent evidence indicates that H+ extrusion in macrophages is in part accomplished by a H(+)-ATPase of vacuolar type. The presence and plasma-membrane localization of such a mechanism in adherent resident macrophages was verified by inhibition of H+ extrusion, monitored by changes in both cytosolic pH (pHi) and extracellular pH, with low concentrations of the H(+)-ATPase inhibitors N-ethylmaleimide and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole. The H(+)-ATPase was operative at physiological pHi levels, thus contributing to maintenance of steady-state pHi. It was further shown to be sensitive to the plasma-membrane potential, with hyperpolarization being strongly inhibitory. In addition, H+ extrusion mediated by the H(+)-ATPase and the generation and release of lactic acid caused acidification of the pericellular space and could enable secreted lysosomal hydrolases to act extracellularly.
authors.affiliation: Department of Medical and Physiological Chemistry, Lund University, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Tapper
authors.forename: R
authors.initials: R
authors.lastname: Sundler
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000494:pharmacology; D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D006180:Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D007773:Lactates; D007770:L-Lactate Dehydrogenase; D000118:Acetylglucosaminidase; D006180:Proton-Translocating ATPases; D009327:4-Chloro-7-nitrobenzofurazan; D016650:Fluorescein-5-isothiocyanate; D005033:Ethylmaleimide