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The chloride channel blocker 5‐nitro‐2‐(3‐phenylpropyl‐amino) benzoic acid (NPPB) uncouples mitochondria and increases the proton permeability of the plasma membrane in phagocytic cells
Author(s) -
Lukacs Gergely L.,
Nanda Arvind,
Rotstein Ori D.,
Grinstein Sergio
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80992-c
Subject(s) - protonophore , chemistry , electrochemical gradient , niflumic acid , channel blocker , biophysics , mitochondrion , cytosol , chloride channel , chemiosmosis , biochemistry , atp synthase , membrane , biology , calcium , enzyme , organic chemistry
We present evidence that the potent chloride channel blocker NPPB has protonophoric activity in the mitochondria and across the plasma membrane of phagocytic cells. The resting O 2 consumption of murine peritoneal macrophages was stimulated up to 2.5‐fold in the presence of NPPB, with a K 0.5 of 15 μM. The stimulatory effect of NPPB also O 2 consumption, like that of the classical protonophore CCCP, was prevented by the mitochondrial respiratory chain inhibitors antimycin A, rotenone or cyanide. NPPB also mediated rheogenic proton transport across the plasma membrane of human neutrophils and macrophages in the direction dictated by the electrochemical proton gradient. As a consequence of its protonophoric activity, NPPB uncoupled mitochondrial ATP synthesis, resulting in partial depletion of cellular ATP. These observations indicate that, at the concentrations frequently used for blockade of anion channels, NPPB acts as an effective protonophore, potentially disturbing cytosolic pH and mitochondrial ATP synthesis.