Preitner F, Muzzin P, Revelli J P, Seydoux J, Galitzky J, Berlan M, Lafontan M, Giacobino J P
Départment de Biochimie Médicale, Centre Médical Universitaire, Geneva, Switzerland.
Br J Pharmacol. 1998 Aug;124(8):1684-8. doi: 10.1038/sj.bjp.0702007.
The beta3-adrenoceptor plays an important role in the adrenergic response of brown and white adipose tissues (BAT and WAT). In this study, in vitro metabolic responses to beta-adrenoceptor stimulation were compared in adipose tissues of beta3-adrenoceptor knockout and wild type mice. The measured parameters were BAT fragment oxygen uptake (MO2) and isolated white adipocyte lipolysis. In BAT of wild type mice (-)-norepinephrine maximally stimulated MO2 4.1+/-0.8 fold. Similar maximal stimulations were obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (dobutamine 5.1+/-0.3, terbutaline 5.3+/-0.3 and CL 316,243 4.8+/-0.9 fold, respectively); in BAT of beta3-adrenoceptor knockout mice, the beta1- and beta2-responses were fully conserved. In BAT of wild type mice, the beta1/beta2-antagonist and beta3-partial agonist CGP 12177 elicited a maximal MO2 response (4.7+/-0.4 fold). In beta3-adrenoceptor knockout BAT, this response was fully conserved despite an absence of response to CL 316,243. This unexpected result suggests that an atypical beta-adrenoceptor, distinct from the beta1-, beta2- and beta3-subtypes and referred to as a putative beta4-adrenoceptor is present in BAT and that it can mediate in vitro a maximal MO2 stimulation. In isolated white adipocytes of wild type mice, (-)-epinephrine maximally stimulated lipolysis 12.1+/-2.6 fold. Similar maximal stimulations were obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (TO509 12+/-2, procaterol 11+/-3, CL 316,243 11+/-3 fold, respectively) or with CGP 12177 (7.1+/-1.5 fold). In isolated white adipocytes of beta3-adrenoceptor knockout mice, the lipolytic responses to (-)epinephrine, to the beta1-, beta2-, beta3-adrenoceptor selective agonists and to CGP 12177 were almost or totally depressed, whereas those to ACTH, forskolin and dibutyryl cyclic AMP were conserved.
β3肾上腺素能受体在棕色和白色脂肪组织（BAT和WAT）的肾上腺素能反应中起重要作用。在本研究中，比较了β3肾上腺素能受体敲除小鼠和野生型小鼠脂肪组织对β肾上腺素能受体刺激的体外代谢反应。测量参数为BAT片段氧摄取量（MO2）和分离的白色脂肪细胞脂解作用。在野生型小鼠的BAT中，（-）去甲肾上腺素最大程度地刺激MO2达4.1±0.8倍。β1、β2或β3肾上腺素能受体选择性激动剂也能产生类似的最大刺激作用（多巴酚丁胺为5.1±0.3倍、特布他林为5.3±0.3倍、CL 316,243为4.8±0.9倍）；在β3肾上腺素能受体敲除小鼠的BAT中，β1和β2反应完全保留。在野生型小鼠的BAT中，β1/β2拮抗剂和β3部分激动剂CGP 12177引发最大MO2反应（4.7±0.4倍）。在β3肾上腺素能受体敲除的BAT中，尽管对CL 316,243无反应，但该反应完全保留。这一意外结果表明，BAT中存在一种不同于β1、β2和β3亚型的非典型β肾上腺素能受体，称为假定的β4肾上腺素能受体，它可在体外介导最大MO2刺激。在野生型小鼠分离的白色脂肪细胞中，（-）肾上腺素最大程度地刺激脂解作用达12.1±2.6倍。β1、β2或β3肾上腺素能受体选择性激动剂（分别为TO509 12±2倍、丙卡特罗11±3倍、CL 316,243 11±3倍）或CGP 12177（7.1±1.5倍）也能产生类似的最大刺激作用。在β3肾上腺素能受体敲除小鼠分离的白色脂肪细胞中，对（-）肾上腺素、β1、β2、β3肾上腺素能受体选择性激动剂和CGP 12177的脂解反应几乎或完全受到抑制，而对促肾上腺皮质激素、福斯高林和二丁酰环磷腺苷的反应则保留。
