Noradrenaline induces brown adipocytes cell growth via beta-receptors by a mechanism dependent on ERKs but independent of cAMP and PKA.
It has been well established that the key role of noradrenaline is the induction of uncoupling-protein-1 (UCP-1) expression, the unique marker of brown adipocytes. However, its implication on proliferation and the pathways involved are not as well characterized. By using rat fetal brown adipocytes as a model, we show that, although noradrenaline activates extracellular regulated kinases (ERKs) through beta-, alpha1-, and alpha2-receptors, only beta-receptors mediate cell growth by a mechanism that requires ERKs activation 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 differentiation. On the other hand, alpha1- and alpha2-receptors have an antiproliferative effect that is enhanced by ERK inhibition.
Valladares
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A
Departamento de Bioquímica y Biología Molecular II, Instituto de Bioquímica, Centro Mixto del Consejo Superior de Investigaciones Científicas y de la Universidad Complutense de Madrid, Madrid, Spain. maporras@eucmax.sim.ucm.es
Porras
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A
Alvarez
A M
AM
Roncero
C
C
Benito
M
M
D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000502:physiology; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009638:Norepinephrine