Tamoxifen does not inhibit the swell activated chloride channel in human neutrophils during the respiratory burst.
Effective functioning of neutrophils relies upon electron translocation through the NADPH oxidase (NOX). The electron current generated (I(e)) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential in activated human neutrophils. Swelling activated chloride channels have been demonstrated in part to counteract the depolarisation generated by the NADPH oxidase I(e). In the present study, the effects of inhibitors of swell activated chloride channels on ROS production and on the swelling activated chloride conductance was investigated in activated human neutrophils. Tamoxifen (10 microM), a specific inhibitor for swell activated chloride channels in neutrophils, completely inhibited both the PMA and FMLP stimulated respiratory burst. This inhibition of the neutrophil respiratory burst was not due to the blocking effect of tamoxifen on the swelling activated chloride conductance in these cells. These results demonstrate that a tamoxifen insensitive swell activated chloride channel has important significance during the neutrophil respiratory burst.
Ahluwalia
Jatinder
J
Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E154LZ, UK. j.ahluwalia@uel.ac.uk
D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010693:Phloretin / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014220:Trialkyltin Compounds / Q000494:pharmacology
D018118:Chloride Channels; D014220:Trialkyltin Compounds; D013629:Tamoxifen; D013481:Superoxides; D005576:Colforsin; C011559:tributyltin; C016658:phorbolol myristate acetate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate; C047983:1,9-dideoxyforskolin; D010693:Phloretin