研究人员发现，在小鼠前庭核中，血管紧张素转换酶（ACE）会降解一种非常规的脑啡肽，即Met-enkephalin-Arg-Phe。ACE的抑制增强了Met-enkephalin-Arg-Phe对μ阿片受体的激活，使表达Drd1多巴胺受体的中棘投射神经元上的谷氨酸释放受到细胞类型特异性的长期抑制。全身性ACE抑制没有内在的奖励性，但减少了芬太尼给药引起的条件性场所偏好，并增强了互惠的社会互动。
这些研究结果提出了一个诱人的前景，即中枢ACE抑制可以促进内源性阿片类药物的信号传递来获得临床益处，同时减轻成瘾的风险。
据介绍，ACE通过切割血管紧张素I产生血管紧张素II来调节血压。在大脑中，ACE在纹状体组织中特别丰富，但ACE在纹状体回路中的功能仍然知之甚少。
附：英文原文
Title: Angiotensin-converting enzyme gates brain circuit–specific plasticity via an endogenous opioid
Author: Brian H. Trieu, Bailey C. Remmers, Carlee Toddes, Dieter D. Brandner, Emilia M. Lefevre, Adrina Kocharian, Cassandra L. Retzlaff, Rachel M. Dick, Mohammed A. Mashal, Elysia A. Gauthier, Wei Xie, Ying Zhang, Swati S. More, Patrick E. Rothwell
Issue&Volume: 2022-02-24
Abstract: Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is especially abundant in striatal tissue, but the function of ACE in striatal circuits remains poorly understood. We find that ACE degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, in the nucleus accumbens of mice. ACE inhibition enhanced mu opioid receptor activation by Met-enkephalin-Arg-Phe, causing a cell type-specific long-term depression of glutamate release onto medium spiny projection neurons expressing the Drd1 dopamine receptor. Systemic ACE inhibition was not intrinsically rewarding, but decreased the conditioned place preference caused by fentanyl administration, and enhanced reciprocal social interaction. Our results raise the enticing prospect that central ACE inhibition can boost endogenous opioid signaling for clinical benefit, while mitigating risk of addiction.
DOI: abl5130
Source: https://www.science.org/doi/10.1126/science.abl5130