The life and times of endogenous opioid peptides: Updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder.
The life and times of endogenous opioid peptides: Updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder.
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DOI：
10.1016/j.neuropharm.2022.109376
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发表时间：
2023-03-01
影响因子：
4.7
通讯作者：
O'Meara, Matthew J.
中科院分区：
文献类型：
--
作者：
Margolis, Elyssa B.;Moulton, Madelyn G.;Lambeth, Philip S.;O'Meara, Matthew J.
阿片G蛋白偶联受体(GPCRs)强烈调节许多中枢神经系统结构，这些结构导致神经和精神疾病，包括疼痛、严重抑郁障碍和物质使用障碍。为了更好地治疗这些疾病和相关疾病，了解它们的内源性配体的信号转导是至关重要的。在这篇综述中，我们重点介绍了对一个或多个阿片受体具有高亲和力的二十多个内源性多肽的调节的已知和未知。我们简要地描述了产生哪些多肽，特别是最近提出的内吗啡素的可能合成途径。接下来，我们描述了几个神经回路中内源性阿片肽表达组织的例子，以及它们是如何从不同大脑区域的特定神经室释放出来的。我们讨论了目前关于驱动内源性阿片肽释放所需的神经活动强度的知识，关于多肽从释放部位扩散到多远的线索，以及它们释放后的细胞外寿命。最后，作为一个翻译的例子，我们讨论了纳曲酮(NTX)的作用机制，它被临床用于治疗酒精使用障碍。NTX是一种合成的吗啡类似物，非特异性拮抗20世纪60年代开发的大多数内源性阿片肽的作用，FDA于80年代批准。我们回顾了最近的研究，阐明了NTX所阻止的确切的内源性活动。总之，这里描述的工作突出了复杂的阿片系统作为治疗靶点带来的挑战和机遇。
The opioid G-protein coupled receptors (GPCRs) strongly modulate many of the central nervous system structures that contribute to neurological and psychiatric disorders including pain, major depressive disorder, and substance use disorders. To better treat these and related diseases, it is essential to understand the signaling of their endogenous ligands. In this review, we focus on what is known and unknown about the regulation of the over two dozen endogenous peptides with high affinity for one or more of the opioid receptors. We briefly describe which peptides are produced, with a particular focus on the recently proposed possible synthesis pathways for the endomorphins. Next, we describe examples of endogenous opioid peptide expression organization in several neural circuits and how they appear to be released from specific neural compartments that vary across brain regions. We discuss current knowledge regarding the strength of neural activity required to drive endogenous opioid peptide release, clues about how far peptides diffuse from release sites, and their extracellular lifetime after release. Finally, as a translational example, we discuss the mechanisms of action of naltrexone (NTX), which is used clinically to treat alcohol use disorder. NTX is a synthetic morphine analog that non-specifically antagonizes the action of most endogenous opioid peptides developed in the 1960s and FDA approved in the 1980s. We review recent studies clarifying the precise endogenous activity that NTX prevents. Together, the works described here highlight the challenges and opportunities the complex opioid system presents as a therapeutic target.
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DOI：
10.1111/j.1530-0277.2011.01535.x
发表时间：
2011-11-01
影响因子：
3.2
作者：
Altamirano, Lee J.;Fields, Howard L.;Boettiger, Charlotte A.
通讯作者：
Boettiger, Charlotte A.
影响因子：
7.7
作者：
Beauchamp A;Yee Y;Darwin BC;Raznahan A;Mars RB;Lerch JP
通讯作者：
Lerch JP
影响因子：
2.9
作者：
Aicher, SA;Mitchell, JL;Zadina, JE
通讯作者：
Zadina, JE
影响因子：
3.4
作者：
Balerio, GN;Aso, E;Maldonado, R
通讯作者：
Maldonado, R
影响因子：
3.3
作者：
Avenali, Luca;Fulas, Oli Abate;Schmidt, Manuela
通讯作者：
Schmidt, Manuela