Phosphorylation of extracellular signal-regulated kinases 1 and 2 in 3T3-L1 adipocytes by stimulation of beta(3)-adrenoceptor.
Recent studies have revealed that activated extracellular signal-regulated kinases (ERKs) 1 and 2 by the stimulation of beta(3)-adrenoceptors played a critical role in cell survival in brown adipocytes. On the other hand, phosphorylation of ERK1/2 via beta(3)-adrenoceptors and its physiological and pathological significance in white adipocyte has remained uncertain despite the increasing significance of functioning white adipocytes. Accordingly, we here studied phosphorylation of ERK1/2 caused by the stimulation of beta(3)-adrenoceptors in 3T3-L1 adipocytes, and the roles of phosphorylated ERK1/2 in lipolysis. Phosphorylation of ERK1/2 was induced by a selective beta(3)-adrenoceptor agonist, DL-4-[2'-¿2-hydroxy-2-(3-chlorophenyl)ethylamino¿propyl] phenoxyacetic acid sodium salt sesquihydrate (BRL37344), in 3T3-L1 adipocytes in a time- and dose-dependent manner. The phosphorylation of ERK1/2 by BRL37344 was sensitive to the cyclic AMP (cAMP)-dependent protein kinase inhibitor, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H89). To elucidate the roles of phosphorylated ERK1/2 in lipolysis, the effect of a selective inhibitor of ERK1/2 phosphorylation, 2'-amino-3'-methoxyflavone (PD98059), was examined. This inhibitor did not alter the lipolytic action caused by BRL37344, even at concentrations sufficient to block phosphorylation of ERK1/2, suggesting that ERK1/2 play no role in the lipolysis caused by BRL37344 in 3T3-L1 adipocytes.
Mizuno
K
K
Department of Pharmacology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Japan.
Kanda
Y
Y
Kuroki
Y
Y
Tomiyama
K
K
Watanabe
Y
Y
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D005419:Flavonoids; D007546:Isoquinolines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes; C057368:BRL 37344; D011433:Propranolol; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D005990:Glycerol; C076252:amibegron; C033394:CGP 12177; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one