Noradrenaline induces brown adipocytes cell growth via beta-receptors by amechanism dependent on ERKs but independent of cAMP and PKA

It has been well established that the key role of noradrenaline is the indu ction of uncoupling-protein-1 (UCP-1) expression, the unique marker of brow n adipocytes. However, its implication on proliferation and the pathways in volved are not as well characterized. By using rat fetal brown adipocytes a s a model, we show that, although noradrenaline activates extracellular reg ulated kinases (ERKs) through beta-, alpha1-, and alpha2-receptors, only be ta -receptors mediate cell growth by a mechanism that requires ERKs activat ion but is independent of cyclic-adenosine-monophosphate/protein kinase A ( cAMP/PKA). Conversely, the cAMP/PKA cascade mediates noradrenaline-induced UCP-1 expression, whereas ERKs pathway attenuates thermogenic differentiati on. On the other hand, alpha1- and alpha2-receptors have an antiproliferati ve effect that is enhanced by ERK inhibition. J. Cell. Physiol. 185:324-330 , 2000. (C) 2000 Wiley-Liss, Inc.