title: Functional consequences of constitutively active alpha2A-adrenergic receptor expression in 3T3F442A preadipocytes and adipocytes.
abstract: 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.
authors.affiliation: I.N.S.E.R.M U317, Institut Fédératif de Recherches Louis Bugnard, Université Paul Sabatier, CHU Rangueil, Toulouse, France.
authors.forename: S
authors.initials: S
authors.lastname: Bétuing
authors.forename: P
authors.initials: P
authors.lastname: Valet
authors.forename: S
authors.initials: S
authors.lastname: Lapalu
authors.forename: D
authors.initials: D
authors.lastname: Peyroulan
authors.forename: G
authors.initials: G
authors.lastname: Hickson
authors.forename: D
authors.initials: D
authors.lastname: Daviaud
authors.forename: M
authors.initials: M
authors.lastname: Lafontan
authors.forename: J S
authors.initials: JS
authors.lastname: Saulnier-Blache
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D016895:Culture Media, Serum-Free; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D016297:Mutagenesis, Site-Directed; D019000:Phosphotyrosine / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012965:Sodium Chloride / Q000494:pharmacology; D014162:Transfection
chemical_list: C547768:ADRA2A protein, human; C547769:Adra2a protein, mouse; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D016895:Culture Media, Serum-Free; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D006165:Guanylyl Imidodiphosphate; D012965:Sodium Chloride; D000068438:Brimonidine Tartrate; C058525:2-methoxyidazoxan; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D019329:Idazoxan