α2 adrenergic receptor dysregulation in depressive disorders: implications for the neurobiology of depression and antidepressant therapy.
α2 adrenergic receptor dysregulation in depressive disorders: implications for the neurobiology of depression and antidepressant therapy.
复制标题
DOI：
10.1016/j.neubiorev.2012.07.011
复制
发表时间：
2012-11
影响因子：
8.2
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Cottingham C;Wang Q
长期以来，去甲肾上腺素能神经传递功能障碍一直被认为发生在抑郁障碍中。α-2肾上腺素能受体(AR)家族作为一组调节去甲肾上腺素系统的关键分子，参与了抑郁症的神经生物学和抗抑郁治疗机制的研究。然而，由于文献中存在明显相互矛盾的发现，抑郁障碍中α2ARs的清晰图景尚未建立。在这篇文章中，我们报告说，仔细考虑文献中的方法学差异可以解决目前在α2AR参与抑郁症方面缺乏共识的问题。特别是，用于确定受体密度的放射性配基(例如激动剂与拮抗剂)的药理学性质在决定研究结果方面至关重要。在抑郁症患者中，放射性标记的激动剂而不是拮抗剂检测到的α2AR密度上调表明高亲和力构象状态α2AR的密度选择性增加，这表明G蛋白与受体的偶联增强。重要的是，这种高亲和力状态的α2AR上调可以通过抗抑郁药物治疗而正常化。因此，抑郁症似乎与α2AR敏感性和反应性增加有关，这可能是抑郁症中假定的去甲肾上腺素能功能障碍的生理学基础。此外，我们还回顾了抑郁症中一些关键的α2AR辅助蛋白的变化，并讨论了它们在α2AR功能障碍中的潜在作用。
Dysfunction in noradrenergic neurotransmission has long been theorized to occur in depressive disorders. The α2 adrenergic receptor (AR) family, as a group of key players in regulating the noradrenergic system, has been investigated for involvement in the neurobiology of depression and mechanisms of antidepressant therapies. However, a clear picture of the α2ARs in depressive disorders has not been established due to the existence of apparently conflicting findings in the literature. In this article, we report that a careful accounting of methodological differences within the literature can resolve the present lack of consensus on involvement of α2ARs in depression. In particular, the pharmacological properties of the radioligand (e.g. agonist versus antagonist) utilized for determining receptor density are crucial in determining study outcome. Upregulation of α2AR density detected by radiolabeled agonists but not by antagonists in patients with depressive disorders suggests a selective increase in the density of high-affinity conformational state α2ARs, which is indicative of enhanced G protein coupling to the receptor. Importantly, this high-affinity state α2AR upregulation can be normalized with antidepressant treatments. Thus, depressive disorders appear to be associated with increased α2AR sensitivity and responsiveness, which may represent a physiological basis for the putative noradrenergic dysfunction in depressive disorders. In addition, we review changes in some key α2AR accessory proteins in depressive disorders and discuss their potential contribution to α2AR dysfunction.
登录
查看更多内容
影响因子：
4.7
作者：
Cottingham C;Li X;Wang Q
通讯作者：
Wang Q
DOI：
10.1017/s1461145709991088
发表时间：
2010-10-01
影响因子：
4.8
作者：
Dwyer, Jason M.;Platt, Brian J.;Beyer, Chad E.
通讯作者：
Beyer, Chad E.
影响因子：
5
作者：
Canciani, Luca;Giaroni, Cristina;Frigo, Gianmario
通讯作者：
Frigo, Gianmario
影响因子：
2.9
作者：
DePaermentier, F;Mauger, JM;Horton, RW
通讯作者：
Horton, RW
DOI：
10.1124/jpet.106.118935
发表时间：
2007-05-01
影响因子：
3.5
作者：
Deupree, Jean D.;Reed, Abbey L.;Bylund, David B.
通讯作者：
Bylund, David B.