Tanaka Masaki, Watanabe Yoshihisa
Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Front Neurosci. 2020 Jan 14;13:1390. doi: 10.3389/fnins.2019.01390. eCollection 2019.
Serotonin 2C receptor (5-HT R) belongs to the superfamily of seven transmembrane domain receptors coupled to G proteins (GPCR). It is broadly distributed in the CNS and its expression is relatively high in the limbic system including the amygdala, nucleus accumbens (NAc), hippocampus, and hypothalamus. Based on its expression patterns and numerous pharmacological studies, 5-HT R is thought to be involved in various brain functions including emotion, appetite, and motor behavior. Here, we review 5-HT R and its relationship with alcohol intake with a particular focus on the involvement of 5-HT R mRNA editing and its association with alcohol preference in mice. RNA editing is a post-transcriptional modification mechanism. In mammals, adenosine is converted to inosine by the deamination enzymes ADAR1 and ADAR2. 5-HT R is the only GPCR subjected to RNA editing within the coding region. It has five editing sites in exon 5 that encode the second intracellular loop. Consequently, three amino acids residues (I156, N158, and I160) of the unedited receptor (INI) may be altered to differently edited isoforms, resulting in a change of receptor activity such as 5-HT potency and G-protein coupling. 5-HT R in the NAc is involved in enhanced alcohol drinking after chronic alcohol exposure and alterations in 5-HT R mRNA editing is important in determining the alcohol preference using different strains of mice and genetically modified mice. RNA editing of this receptor may participate in the development of alcoholism.
血清素2C受体（5-HT₂C R）属于与G蛋白偶联的七跨膜结构域受体超家族（GPCR）。它广泛分布于中枢神经系统，在包括杏仁核、伏隔核（NAc）、海马体和下丘脑在内的边缘系统中表达相对较高。基于其表达模式和众多药理学研究，5-HT₂C R被认为参与了包括情绪、食欲和运动行为在内的各种脑功能。在此，我们综述5-HT₂C R及其与酒精摄入的关系，特别关注5-HT₂C R mRNA编辑的参与情况及其与小鼠酒精偏好的关联。RNA编辑是一种转录后修饰机制。在哺乳动物中，腺苷通过脱氨酶ADAR1和ADAR2转化为次黄嘌呤。5-HT₂C R是唯一在编码区内受到RNA编辑的GPCR。它在编码第二个细胞内环的外显子5中有五个编辑位点。因此，未编辑受体（INI）的三个氨基酸残基（I156、N158和I160）可能会改变为不同的编辑异构体，从而导致受体活性的变化，如5-HT效力和G蛋白偶联。NAc中的5-HT₂C R参与慢性酒精暴露后酒精摄入量的增加，并且5-HT₂C R mRNA编辑的改变在使用不同品系小鼠和基因改造小鼠确定酒精偏好方面很重要。该受体的RNA编辑可能参与酒精中毒的发展。
