title: Inhibition of fMLP-triggered respiratory burst of human monocytes by adenosine: involvement of A3 adenosine receptor.
abstract: Adenosine (Ado) is a potent anti-inflammatory agent acting on a variety of cell functions. However, its effects on human monocytes have been less well characterized. We investigated the effect of Ado and its receptor-specific analogs on NADPH oxidase activity with the use of luminol-enhanced chemiluminescence (CL). Adenosine inhibited fMLP-triggered NADPH oxidase activity with a maximal inhibition of 55+/-5%. IB-MECA, a selective A3 Ado receptor agonist reduced fMLP triggered NADPH oxidase activity more potently than the A2 receptor agonist CGS 2180 HCl (CGS) and the A1 Ado receptor agonist N-2-phenylethyl-adenosine (R-PIA). The inhibitory effect of Ado was reversed by neither the A1 Ado receptor antagonist 1,3-dipropyl-8(2-amino-4chlorophenyl)-xanthine (PACPX) nor the A2 Ado receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine (DMPX). It was significantly reversed by the A1/A3 Ado receptor antagonist xanthine amine congener (XAC). Pretreatment of monocytes by cytochalasin B reversed the effect of Ado but not of dibutyryl cAMP (dBcAMP) on fMLP-CL response. KT 5720, a specific cAMP-dependent protein kinase inhibitor completely counteracted the inhibition of NADPH oxidase activity by dBcAMP but not by Ado. Using flow cytometry, we observed that Ado did not inhibit intracellular oxidative metabolism, whereas dBcAMP did. Furthermore, the inhibition of NADPH oxidase activity by Ado was not mediated by changes in cytosolic calcium. These results demonstrated that Ado inhibited NADPH oxidase activity via A3 Ado receptor independently of cAMP elevation or changes in calcium mobilization.
authors.affiliation: UPRES EA2070, Laboratoire d'Immunologie et d'Hématologie, IFR 53 (Biomolécules), Reims, France.
authors.forename: M
authors.initials: M
authors.lastname: Broussas
authors.forename: P
authors.initials: P
authors.lastname: Cornillet-Lefèbvre
authors.forename: G
authors.initials: G
authors.lastname: Potron
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002227:Carbazoles; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D003571:Cytochalasin B / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008163:Luminescent Measurements; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects*; D015290:Second Messenger Systems / Q000187:drug effects; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D012333:RNA, Messenger; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D014970:Xanthines; D003571:Cytochalasin B; C057416:KT 5720; D009240:N-Formylmethionine Leucyl-Phenylalanine; C057837:3,7-dimethyl-1-propargylxanthine; D003994:Bucladesine; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; D000242:Cyclic AMP; D019255:NADPH Oxidases; D017868:Cyclic AMP-Dependent Protein Kinases; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D000241:Adenosine; D013805:Theobromine; D002118:Calcium