Inhibition of LPS-induced TNF alpha production in human monocytes by adenosine (A2) receptor selective agonists.
We examined the effects of adenosine A1 and A2 receptor agonists on LPS-stimulated TNF alpha production by human monocytes isolated from peripheral blood. We have demonstrated that CGS-21680, a highly selective A2 agonist inhibited production of TNF alpha at the protein level by 75% whereas the A1 selective agonist N6 reduced TNF alpha production by only 25%. The action of CGS-21680 was mediated via the A2 receptors since its effect on TNF production was blocked by 3,7-dimethyl-1-propargylxanthine (DMPX) but not by xanthine amine cogener (XAC), antagonists selective for the A2 and A1 receptors, respectively. Thus intervention with A2-selective agonists or compounds that can elevate endogenously released adenosine may be beneficial in TNF alpha-mediated diseases.
Prabhakar
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Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Brooks
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Lipshlitz
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Esser
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D002478:Cells, Cultured; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014970:Xanthines / Q000494:pharmacology
D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D014409:Tumor Necrosis Factor-alpha; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; D013805:Theobromine