Multiple G-protein-coupling specificity of β-adrenoceptor in macrophages

• Published in: Immunology 2007-12, Vol.122 (4), p.503-513
• Main Authors: Magocsi, Maria, Vizi, E. Sylvester, Selmeczy, Zsolt, Brózik, Anna, Szelenyi, Judith
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - pharmacology; Animals; Enzyme Activation - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; G-proteins; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; GTP-Binding Protein alpha Subunits, Gs - metabolism; GTP-Binding Proteins - metabolism; Isoproterenol - pharmacology; Lipopolysaccharides - immunology; macrophages; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; MAP kinases; Mice; Mice, Inbred BALB C; Original; p38 Mitogen-Activated Protein Kinases - metabolism; Pertussis Toxin - immunology; Phosphorylation - drug effects; Receptors, Adrenergic, beta - metabolism; Signal Transduction - immunology; Tetradecanoylphorbol Acetate - immunology; TNF-α; Tumor Necrosis Factor-alpha - biosynthesis; β-adrenoceptor
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2007.02658.x

Adrenergic signalling of the immune system is one of the important modulator pathways of the inflammatory immune response realized via G protein-mediated pathways. The resulted signal depends on the type of the receptor-coupled G-protein (GPCR) that, according to the classical paradigm in the case of β-adrenergic receptor (β-AR), is Gs-type. Recently, alternate and/or multiple G protein coupling specificity of GPCRs have been demonstrated including a switch from Gs to Gi binding. The possibility of a Gs/Gi switch and its role in the immune response of macrophages has not been investigated yet. In this study, we demonstrate that β-adrenergic stimulation itself is able to induce a transient mitogen-activated protein kinase phosphorylation in murine peritoneal macrophages in a pertussis toxin-sensitive manner, suggesting that the Gs/Gi switch also occurs in the immune system. Although this process is very rapid, it can influence different signalling pathways and can reprogramme effector functions suggesting that sympathetic modulation of the defence mechanism of the innate immune system has an additional, Gs/Gi switch-dependent component.