Sub‐types of serotonin receptors: biochemical changes and pharmacological consequences
Sub‐types of serotonin receptors: biochemical changes and pharmacological consequences
复制标题
血清素受体的亚型：生化变化和药理学后果
DOI：
10.1097/00004850-199200710-00002
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发表时间：
1992
影响因子：
2.6
通讯作者：
B. Leonard
中科院分区：
文献类型：
--
作者：
B. Leonard
患者;33年前，Gaddum和Picarelli根据二苄啉和吗啡的活性将豚鼠回肠中的5 -羟色胺受体分为D型和M型，以阻止5 -羟色胺引起的肠平滑肌收缩。随后对大脑中5 -羟色胺的特定配体结合位点的定位导致了在大鼠脑中至少8种5 -羟色胺受体亚型的鉴定。虽然对这些受体亚型的功能重要性存在一些争议，但有证据表明，根据它们与次级信使或离子通道耦合的性质，它们可分为两大类。因此，5‐HT1和5‐HT2受体似乎占据了G蛋白受体亚家族，该亚家族可能与腺苷酸环化酶（大多数5‐HT1亚型）或磷脂酰肌醇（5‐HT2亚型）偶联。中心“M”受体（现在称为5‐HT3）似乎占据了一个配体门控离子通道超家族。1989年克隆的3种5 -羟色胺受体亚型（5 - HT1A， 5 - HT1C和5 - HT2）对于将受体亚型分类为由特定基因编码的特定蛋白质分子具有重要意义。现在出现的问题是，各种受体亚型的细胞活性变化与大脑中血清素作用导致的过多行为变化之间的联系。本文综述了有关特定5 -羟色胺受体亚型在饮食失调、睡眠、性活动、焦虑状态、攻击、精神分裂症和抑郁症中作用的证据。表2总结了这些受体亚型之间的关系及其可能参与这些疾病的病因学。
&NA; Thirty‐three years ago, Gaddum and Picarelli classified the serotonin receptors in the guinea pig ileum into D and M types based on the activity of dibenzyline and morphine to block contractions of intestinal smooth muscle caused by serotonin. The subsequent location of specific ligand binding sites for serotonin in the brain has led to the identification of at least eight serotonin receptor sub‐types in rat brain. While there is some controversy over the functional importance of many of these receptor sub‐types, there is evidence that they fall into two major groups according to the nature of their coupling to secondary messengers or ion channels. Thus the 5‐HT1 and 5‐HT2 receptors appear to occupy the G protein receptor sub‐family which may be coupled either to adenylate cyclase (most 5‐HT1 sub‐types) or phosphatidyl inositol (5‐HT2 sub‐types). The central “M” receptors (now termed 5‐HT3) appear to occupy a ligand gated ion channel super‐family. The cloning of three of the serotonin receptor sub‐types in 1989 (5‐HT1A, 5‐HT1C and 5‐HT2) has been of importance in enabling the receptor sub‐types to be classified as specific protein molecules encoded by specific genes. The problem now arises with regard to the linking of the changes in the cellular activity of the various receptor sub‐types with the plethora of behavioural changes that arise as a consequence of the actions of serotonin in the brain. The present review summarizes the evidence implicating the role of specific serotonin receptor sub‐types in eating disorders, sleep, sexual activity, anxiety states, aggression, schizophrenia and depression. A summary of the relationship between these receptor sub‐types and their possible involvement in the aetiology of these diseases is shown in Table 2.