title: Relationship between calcium release and NADPH oxidase inhibition in human neutrophils.
abstract: The aim of this study was to investigate the possible relationship between NADPH oxidase activity and changes in cytosolic Ca(2+) in response to different agonists. Treatment of neutrophils with leukotriene B4 (LTB(4)) demonstrated characteristic changes to cytoslic Ca(2+) yielding an EC(50) of 4nM. The pA(2) values for the specific LTB(4) receptor (BLT) antagonists, U-75302 and LY-255283 were 6.32 and 6.38, respectively. Similarly, neutrophils treated with N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) and platelet activating factor (PAF) exhibited changes in cytoslic Ca(2+) in a dose dependant manner with pD(2) values of 9.0 and 9.9, respectively. The phorbol ester PMA prevented elevations in cytosolic Ca(2+) in response to LTB(4), FMLP and PAF with IC(50) values of 5.88, 1.44 and 5.71nM, respectively. In addition, potent NADPH oxidase inhibitors apocynin and diphenyleneiodonium (DPI) inhibited FMLP mediated cytosolic Ca(2+) release. These results demonstrate that inhibition of the NADPH oxidase suppresses cytosolic Ca(2+) release in FMLP activated human neutrophils.
authors.affiliation: Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, London, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Salmon
authors.forename: Jatinder
authors.initials: J
authors.lastname: Ahluwalia
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005233:Fatty Alcohols / Q000494:pharmacology; D006018:Glycols / Q000494:pharmacology; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D005233:Fatty Alcohols; D006018:Glycols; D020024:Leukotriene Antagonists; D018102:Receptors, Leukotriene B4; D013777:Tetrazoles; C062137:U 75302; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; C063823:LY 255283; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium