α1-adrenergic stimulation potentiates the thermogenic action of β3-adrenoreceptor-generated cAMP in brown fat cells
α1-adrenergic stimulation potentiates the thermogenic action of β3-adrenoreceptor-generated cAMP in brown fat cells
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DOI：
10.1074/jbc.272.52.32847
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发表时间：
1997-12-26
影响因子：
4.8
通讯作者：
Nedergaard, J
中科院分区：
文献类型：
--
作者：
Zhao, J;Cannon, B;Nedergaard, J
在叙利亚仓鼠的棕色脂肪细胞中，cAMP水平和生热作用之间的关系被研究了，无论是选择性的β(3)、β(2)和β(1)激动剂BRL 37344、沙丁胺醇和多巴酚丁胺或生理激动剂去甲肾上腺素用于刺激细胞，cAMP水平的增加是通过β(3)受体介导的，生热效应也是如此，然而，对于除去甲肾上腺素之外的其他药物，cAMP水平的关系要低得多，类似地，Forsklin虽然在升高cAMP方面比去甲肾上腺素更有效，但在诱导发热方面效果较差。选择性的α(1)激动剂Crazoline本身对cAMP水平或生热作用没有影响，但当加入Forsklin刺激的细胞中时，促进生热作用，直到去甲肾上腺素水平，而不影响cAMP。这种增强不能被白屈菜红碱抑制，但可以被钙离子载体模拟，它显然不是通过钙调素依赖的蛋白激酶介导的，对线粒体呼吸控制没有影响。所有cAMP提高剂诱导棕色脂肪细胞产热的能力早先被解释为仅通过β-受体和由此导致的cAMP水平的增加来诱导产热，然而，这里的结论是去甲肾上腺素的生热反应涉及两个相互作用的部分，一个通过β-受体和cAMP，另一个通过α(1)-受体和胞浆钙水平的增加。
The relationship between cAMP levels and thermogenesis was investigated in brown fat cells from Syrian hamsters, Irrespective of whether the selective beta(3)-, beta(2)-, and beta(1)-agonists BRL 37344, salbutamol, and dobutamine or the physiological agonist norepinephrine was used to stimulate the cells, increases in cAMP levels were mediated via the beta(3)-receptor, as were the thermogenic effects, However, the relationship "thermogenesis per cAMP" was much lower for agents other than norepinephrine, Similarly, forskolin, although more potent than norepinephrine in elevating cAMP, was less potent in inducing thermogenesis, The selective alpha(1)-agonist cirazoline was in itself without effect on cAMP levels or thermogenesis, but when added to forskolin-stimulated cells, potentiated thermogenesis, up to the norepineph rine level, without affecting cAMP. This potentiation could not be inhibited by chelerythrine, but could be mimicked by Ca2+ ionophores, It was apparently not mediated via calmodulin-dependent protein kinase and was not an effect on mitochondrial respiratory control, The ability of all cAMP-elevating agents to induce thermogenesis in brown fat cells has earlier been interpreted to mean that it is only through the beta-receptors and the resulting increase in cAMP levels that thermogenesis is induced, However, it is here concluded that the thermogenic response to norepinephrine involves two interacting parts, one mediated via beta-receptors and cAMP and the other via alpha(1)-receptors and increases in cytosolic Ca2+ levels.