THE INTRIGUING LIGAND-DEPENDENT AND LIGAND-INDEPENDENT ACTIONS OF THE GROWTH HORMONE SECRETAGOGUE RECEPTOR ON REWARD-RELATED BEHAVIORS
THE INTRIGUING LIGAND-DEPENDENT AND LIGAND-INDEPENDENT ACTIONS OF THE GROWTH HORMONE SECRETAGOGUE RECEPTOR ON REWARD-RELATED BEHAVIORS
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DOI：
10.1016/j.neubiorev.2020.10.017
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发表时间：
2021-01-28
影响因子：
8.2
通讯作者：
Perello, Mario
中科院分区：
文献类型：
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作者：
Cornejo, Maria P.;Mustafa, Emilio R.;Perello, Mario
生长激素促分泌素受体(GHSR)是一种G蛋白偶联受体，在大脑和一些外周组织中高度表达。GHSR活性由胃源性多肽激素Ghrelin激发，并被肠源性肝脏表达的抗菌肽2(Leap2)取消。在体外，GHSR表现出不依赖于配体的作用，包括高的结构活性和其他GPCRs的变构调节。除了神经内分泌和代谢作用外，累积证据表明，GHSR还调节中皮质边缘通路的活性，并调节对不同刺激的复杂奖赏相关行为。在这里，我们回顾了目前的证据表明，GHSR的配体依赖和配体非依赖的作用增强了对食欲刺激和滥用药物的奖赏相关行为。我们讨论了GHSR可能参与调节这种奖赏相关行为的神经元网络和分子机制。最后，我们简要讨论了显示Ghrelin也会调节人类奖赏过程的成像研究。总体而言，我们得出结论，GHSR是中皮质边缘通路的关键调节因子，该通路影响其活性，从而通过配体依赖和非配体依赖的作用来调节与奖励相关的行为。
The growth hormone secretagogue receptor (GHSR) is a G-protein-coupled receptor (GPCR) highly expressed in the brain, and also in some peripheral tissues. GHSR activity is evoked by the stomach-derived peptide hormone ghrelin and abrogated by the intestine-derived liver-expressed antimicrobial peptide 2 (LEAP2). In vitro, GHSR displays ligand-independent actions, including a high constitutive activity and an allosteric modulation of other GPCRs. Beyond its neuroendocrine and metabolic effects, cumulative evidence shows that GHSR regulates the activity of the mesocorticolimbic pathway and modulates complex reward-related behaviors towards different stimuli. Here, we review current evidence indicating that ligand-dependent and ligand-independent actions of GHSR enhance reward-related behaviors towards appetitive stimuli and drugs of abuse. We discuss putative neuronal networks and molecular mechanisms that GHSR would engage to modulate such reward-related behaviors. Finally, we briefly discuss imaging studies showing that ghrelin would also regulate reward processing in humans. Overall, we conclude that GHSR is a key regulator of the mesocorticolimbic pathway that influences its activity and, consequently, modulates reward-related behaviors via ligand-dependent and ligand-independent actions.