Bétuing S, Valet P, Lapalu S, Peyroulan D, Hickson G, Daviaud D, Lafontan M, Saulnier-Blache J S
I.N.S.E.R.M U317, Institut Fédératif de Recherches Louis Bugnard, Université Paul Sabatier, CHU Rangueil, Toulouse, France.
Biochem Biophys Res Commun. 1997 Jun 27;235(3):765-73. doi: 10.1006/bbrc.1997.6887.
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.
在3T3F442A前脂肪细胞系中稳定表达的组成型活性突变型（CAM）人α2C10 - 肾上腺素能受体（AR），在脂肪前体细胞和脂肪细胞阶段的功能后果均进行了分析。在脂肪前体细胞阶段，CAMα2C10 - AR（在无激动剂时）重现并（在有激动剂时）放大了激动剂刺激的野生型α2C10 - AR所促进的大部分细胞反应（前脂肪细胞增殖增加、丝裂原活化蛋白激酶的酪氨酸磷酸化、对血清剥夺诱导的细胞收缩的抗性、分化抑制）。相反，在脂肪细胞阶段，CAMα2C10 - AR的表达既未重现也未放大α2 - 肾上腺素能依赖性抗脂解作用，反而导致Gi蛋白的αi亚基下调，并使对脂解剂的最大反应增加。我们的结果表明，CAM受体对细胞内信号的长期激活不仅会导致激动剂刺激的野生型受体通常产生的预期细胞反应，还会导致长期代偿性适应产生的意外反应。
