The pharmacology of sigma-1 receptors.
The pharmacology of sigma-1 receptors.
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DOI：
10.1016/j.pharmthera.2009.07.001
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发表时间：
2009-11
影响因子：
13.5
通讯作者：
Su TP
中科院分区：
文献类型：
--
作者：
Maurice T;Su TP
最初被认为是一种神秘的蛋白质，sigma-1受体最近被确定为细胞内质网中一种独特的配体调节分子伴侣。这一发现使我们回顾该受体的许多被提出的作用，甚至在其分子功能被确定之前，在许多疾病中，如甲基苯丙胺或可卡因成瘾、健忘症、疼痛、抑郁、阿尔茨海默病、中风、视网膜神经保护、艾滋病毒感染和癌症。在这篇综述中，我们研究了在这些疾病的模型中明确显示了关于sigma-1受体的激动剂-拮抗剂关系的报告，并回顾了相对已知的sigma-1受体的作用机制，试图激发读者对内质网sigma-1受体如何与如此多疾病相关的猜测。我们发现sigma-1受体在包括细胞系、原代培养和动物在内的生物系统中最突出的作用是调节和调节电压调节和配体门控离子通道，包括Ca2+-、K+-、Na+、Cl-和SK通道，以及NMDA和IP3受体。我们发现sigma-1受体激动剂的作用最终输出是抑制上述所有电压门控离子通道，同时增强配体门控通道。由激动剂引起的抑制或增强作用被sigma-1受体拮抗剂阻断。我们还考虑了sigma-1受体的其他作用机制，以及在一定程度上sigma-2受体的作用机制。我们得出结论，sigma-1和sigma-2受体代表了对抗许多人类疾病的治疗发展的潜在富有成效的目标。
Originally considered an enigmatic protein, the sigma-1 receptor has recently been identified as a unique ligand-regulated molecular chaperone in the endoplasmic reticulum of cells. This discovery causes us to look back at the many proposed roles of this receptor, even before its molecular function was identified, in many diseases such as methamphetamine or cocaine addiction, amnesia, pain, depression, Alzheimer’s disease, stroke, retinal neuroprotection, HIV infection, and cancer. In this review, we examine the reports that have clearly shown an agonist-antagonist relationship regarding sigma-1 receptors in models of those diseases and also review the relatively known mechanisms of action of sigma-1 receptors in an attempt to spur the speculation of readers on how the sigma-1 receptor at the endoplasmic reticulum might relate to so many diseases. We found that the most prominent action of sigma-1 receptors in biological systems including cell lines, primary cultures, and animals is the regulation and modulation of voltage-regulated and ligand-gated ion channels, including Ca2+-, K+-, Na+, Cl-, and SK channels, and NMDA and IP3 receptors. We found that the final output of the action of sigma-1 receptor agonists is to inhibit all above-mentioned voltage-gated ion channels, while they potentiate ligand-gated channels. The inhibition or potentiation induced by agonists is blocked by sigma-1 receptor antagonists. Other mechanisms of action of sigma-1 receptors, and to some extent those of sigma-2 receptors, were also considered. We conclude that the sigma-1 and sigma-2 receptors represent potential fruitful targets for therapeutic developments in combating many human diseases.
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DOI：
10.1126/science.1166127
发表时间：
2009-02-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fontanilla D;Johannessen M;Hajipour AR;Cozzi NV;Jackson MB;Ruoho AE
通讯作者：
Ruoho AE
DOI：
10.1111/j.1742-7843.2007.00044.x
发表时间：
2007-03-01
影响因子：
3.1
作者：
Bucolo, Claudio;Drago, Filippo
通讯作者：
Drago, Filippo
影响因子：
2.1
作者：
Ajmo, Craig T., Jr.;Vernon, Dionne O. L.;Cuevas, Javier
通讯作者：
Cuevas, Javier
影响因子：
5
作者：
Bucolo, C;Marrazzo, A;Drago, F
通讯作者：
Drago, F
影响因子：
4.4
作者：
Dun, Ying;Thangaraju, Muthusamy;Smith, Sylvia B.
通讯作者：
Smith, Sylvia B.