The stimulation of beta(3)-adrenoceptor causes phosphorylation of extracellular signal-regulated kinases 1 and 2 through a G(s)- but not G(i)-dependent pathway in 3T3-L1 adipocytes.
The treatment of 3T3-L1 adipocytes with three beta(3)-adrenoceptor agonists, (+/-)-(R*, R*)-(4-[2-([2-(3-chlorophenyl)-2-hydroxyethyl]amino)propyl]phenoxy)ac etic acid (BRL37344), 4-[3-[(1, 1-dimethylethyl)amino]-2-hydroxypropoxy]-1, 3-dihydro-2H-benzimidazol-2-one (CGP12177) and [(7S)7-¿(2R)2-(3-chlorophenyl)-2-hydroxyethyl-amino¿-5,6,7, 8-tetrahydronapht-2-yl]ethyl oxyacetate, hydrochloride (SR58611) induces phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). The phosphorylations were not affected by pretreatment of the adipocytes with pertussis toxin, whereas the same treatment completely abolished lisophosphatidic acid-induced phosphorylation of ERK1/2, suggesting the role of pertussis toxin-insensitive G protein in the ERK1/2 phosphorylation by stimulation with the beta(3)-adrenoceptor agonists. The phosphorylation of ERK1/2 was mimicked by treating the adipocytes with cholera toxin, a direct activator of stimulatory G (G(s)) protein. In addition, the ERK1/2 phosphorylations by the beta(3)-adrenoceptor agonists were completely diminished by long-term treatment of the adipocytes with cholera toxin (100 ng/ml, 24 h), whereas that obtained with lisophosphatidic acid stimulation was not. Our findings strongly suggest that the three beta(3)-adrenoceptor agonists induce ERK1/2 phosphorylation in 3T3-L1 adipocytes through a G(s) protein-dependent cascade.
Mizuno
K
K
Department of Pharmacology, National Defense Medical College, 3-2 Namiki, 359-8513, Tokorozawa, Japan.
Kanda
Y
Y
Kuroki
Y
Y
Watanabe
Y
Y
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000322:Adrenergic Agonists / Q000494:pharmacology; D058667:Adrenergic beta-3 Receptor Agonists; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D037342:Pertussis Toxin; D010766:Phosphorylation / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000322:Adrenergic Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D022702:Receptors, Adrenergic, beta-3; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs