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, pho sphorylation 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 ERK 1/2 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 ERK 1/2 by BRL37344 was sensitive to the cyclic AMP (cAMP)-dependent protein ki nase inhibitor, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolnesulfonamid e (H89). To elucidate the roles of phosphorylated ERK1/2 in lipolysis, the effect of a selective inhibitor of ERK1/2 phosphorylation, 2'-amino-3'-meth oxyflavone (PD98059), was examined. This inhibitor did not alter the lipoly tic action caused by BRL37344, even at concentrations sufficient to block p hosphorylation of ERK1/2, suggesting that ERK1/2 play no role in the lipoly sis caused by BRL37344 in 3T3-L1 adipocytes. (C) 1999 Elsevier Science B.V. All rights reserved.