Functional consequences of constitutively active alpha2A-adrenergic receptor expression in 3T3F442A preadipocytes and adipocytes

• Published in: Biochemical and biophysical research communications Vol. 235; no. 3; p. 765
• Main Authors: Bétuing, S, Valet, P, Lapalu, S, Peyroulan, D, Hickson, G, Daviaud, D, Lafontan, M, Saulnier-Blache, J S
• Format: Journal Article
• Language: English
• Published: United States 27.06.1997
• Subjects: 3T3 Cells; Adipocytes - cytology; Adipocytes - metabolism; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Brimonidine Tartrate; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cell Differentiation; Cell Division; Culture Media, Serum-Free; GTP-Binding Proteins - biosynthesis; Guanylyl Imidodiphosphate - pharmacology; Humans; Idazoxan - analogs & derivatives; Idazoxan - pharmacology; Kinetics; Lipolysis - drug effects; Mice; Mutagenesis, Site-Directed; Phosphotyrosine - metabolism; Quinoxalines - pharmacology; Receptors, Adrenergic, alpha-2 - biosynthesis; Receptors, Adrenergic, alpha-2 - physiology; Recombinant Fusion Proteins - biosynthesis; Sodium Chloride - pharmacology; Transfection
• ISSN: 0006-291X

The functional consequences of a constitutively active mutated (CAM) human alpha2C10-adrenergic receptor (AR) stably expressed in the 3T3F442A preadipose cell line were analysed at both preadipocyte and adipocyte stages. At the preadipocyte stage, CAMalpha2C10-AR reproduced (in the absence of agonist) and amplified (in the presence of agonist) most of the cellular responses promoted by agonist-stimulated wild type alpha2C10-AR (increased preadipocyte proliferation, tyrosyl-phosphorylation of the Mitogen Activated Protein Kinases, resistance to serum-deprivation-induced cell retraction, inhibition of differentiation). In contrast, at the adipocyte stage, CAMalpha2C10-AR expression did not reproduced nor amplified the alpha2-adrenergic-dependent antilipolysis, but conversely led to a down-regulation of alpha i subunits of the Gi proteins and to an increase in the maximal response to lipolytic agents. Our results indicate that long term activation of intracellular signals by CAM-receptors not only lead to the expected cellular responses normally generated by agonist-stimulated wild type receptors, but can also lead to unexpected responses resulting from long term compensatory adaptations.