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

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.