5-羟色胺受体

5-羥色胺受體，也被稱為血清素受體或5-HT受體，是一羣於中樞神經系統中央處和末梢神經系統周邊出現的G蛋白偶聯受體及配體門控離子通道。[1][2]它們同時調節興奮性和抑制性神經傳導物質的傳遞。

以5-HT1B 受體 作為代謝型血清素受體的一個例子。其呈現出緞帶狀的晶體結構。

分類

血清素受體可分為七個亞科 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7。至少有十四種受體亞型已被發現，包含G蛋白偶聯受體和配體門控離子通道(G protein-coupled receptor and a ligand-gated ion channe)。

  • 5-HT1受體是5-HT受體家族中最龐大的一科，目前有A、B、D、E、F5種亞型, 5-HT1A、5-HT1B、5-HT1D、5-HT1E、5-HT1F五種受體蛋白。沒有5-HT1C受體，因為它被重新分類為5-HT2C受體。
  • 5-HT2受體次家族有A、B、C, 3種亞型, 5-HT2A、5-HT2B，和5-HT2C三種受體蛋白。
  • 5-HT3受體
  • 5-HT4受體
  • 5-HT5受體次家族有A、B、2種亞型, 5-HT5A、5-HT5B二種受體蛋白。
  • 5-HT6受體
  • 5-HT7受體

總共有十四種受體亞型。

除了5-HT3受体是配体门控离子通道以外，其它的所有血清素受体都是G蛋白偶联受体，激活细胞内的第二信使来产生效应。在2014年，在菜粉蝶基因组中发现了一种新的5-HT受体，被命名为pr5-HT8。它与已知的各类5-HT受体相似度很低，在哺乳动物中没有类似基因。[3]

家族

七個亞科 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7。

家族類型作用機制類別
5-HT1Gi/Go-蛋白偶聯受体減少cAMP在細胞內的水平抑制性
5-HT2Gq/G11-蛋白偶聯受体增加細胞內IP3和DAG的水平興奮性
5-HT3配體門控Na+，K+离子通道使質膜去極化興奮性
5-HT4Gs蛋白偶聯受体增加細胞內cAMP的水平興奮性
5-HT5Gi/Go-蛋白偶聯受体[4]減少cAMP在細胞內的水平抑制性
5-HT6Gs-蛋白偶聯受体增加細胞內cAMP的水平興奮性
5-HT7Gs-蛋白偶聯受体增加細胞內cAMP的水平興奮性

亞型
血清素受體功能概述
受體 首次克隆 基因 分佈 作用 激動劑 拮抗劑 用途
血管 中樞神經系統 胃腸道 血小板 外周神經系統 平滑肌
5-HT1A 1987 是 是 否 否 否 否

選擇性

  • Vilazodone (Viibryd)
  • F-15,599 (research compound, highly potent and selective for 5-HT1A)
  • Flesinoxan (potent, EC50 = 24 nM)
  • Gepirone (部分激动剂, Ki = 70 nM)
  • 氟哌啶醇
  • Ipsapirone (部分激动剂, Ki = 12.1 nM)
  • 喹硫平
  • Trazodone (SARI, selective in the sense that on all other 5-HT receptors it acts as either an antagonist or has no action. Kd = 78nM)
  • 育亨宾 (unselective 部分激动剂)
  • 坦度螺酮 (potent and selective 部分激动剂)

非選擇性

  • 5-CT (potent - Ki = 250±50 pM)
  • 8-OH-DPAT (potent)
  • 阿立哌唑 (atypical antipsychotic)
  • Asenapine (atypical antipsychotic)
  • 丁螺環酮[28]（部分激动剂）
  • Vortioxetine (high-efficacy 部分激动剂)[29]
  • Ziprasidone (部分激动剂, Ki = 3.4 nM)
  • BMY 7378
  • Cyanopindolol
  • Iodocyanopindolol
  • Lecozotan
  • Methiothepin
  • Methysergide[30]
  • NAN-190
  • Nebivolol
  • Nefazodone
  • WAY-100,135
  • WAY-100,635
  • Mefway
  • 镇痛药 (agonists)
  • 抗抑郁药 (post-synaptic receptor agonists and pre-synaptic autoreceptor antagonists serve as antidepressants)
  • Anxiolytics[31] (antagonist)
5-HT1B 1992 是 是 否 否 否 否
  • Alprenolol
  • AR-A000002
  • Asenapine
  • Cyanopindolol
  • GR-127,935
  • Iodocyanopindolol
  • Isamoltane
  • Metergoline
  • Methiothepin
  • Oxprenolol
  • Pindolol
  • 普萘洛尔
  • SB-216,641
  • 育亨宾
5-HT1D 1991 是 是 否 否 否 否
  • BRL-15572
  • GR-127,935
  • Ketanserin
  • Metergoline
  • Methiothepin
  • Rauwolscine
  • Ritanserin
  • Vortioxetine (Ki = 54 nM)[29]
  • Ziprasidone
5-HT1E 1992 是 是 否 否 否 否
  • BRL-54443
  • None known
5-HT1F 1993 否 是 否 否 否 否
  • Migraine
  • BRL-54443
  • Lasmiditan
  • LY-334,370
  • Naratriptan
  • None known
5-HT2A 1988 是 是 是 是 是 是
  • 成瘾 (potentially modulating) [40]
  • 焦虑[41]
  • 食欲
  • Cognition
  • Imagination
  • Learning
  • 记忆
  • 情绪
  • Perception
  • 性行为[42]
  • 睡眠[43]
  • 体温调节[44]
  • 血管收缩[45]
5-HT2B 1992 是 是 是 是 是 是
5-HT2C 1988 是 是 是 是 是 是
5-HT3 1993 否 是 是 否 是 否
  • 成瘾
  • 焦虑
  • Emesis
  • GI Motility[62]
  • Learning[63]
  • 记忆[63]
  • Nausea
5-HT4 1995 否 是 是 否 是 否
  • 5-MT
  • BIMU-8
  • Cinitapride
  • Cisapride[28] (gastroprokinetic)
  • Dazopride
  • Metoclopramide
  • Mosapride
  • Prucalopride
  • RS-67333
  • Renzapride
  • Tegaserod
  • Zacopride
  • Gastroprokinetics (e.g. Tegaserod)
5-HT5A 1994 否 是 否 否 否 否
  • Asenapine
  • Dimebolin
  • Methiothepin
  • Ritanserin
  • SB-699,551
  • SB-699,551-A
  • None thus far
5-HT5B 1993 否 否 否 否 否 否

Functions in rodents,
pseudogene in humans
  • None thus far
5-HT6 1993 否 是 否 否 否 否
  • EMD-386,088
  • EMDT
  • Antidepressant (antagonists and agonists)
  • Anxiolytic (antagonists and agonist)
  • Nootropic (antagonists)
  • Anorectic (antagonists)
5-HT7 1993 是 是 是 否 否 否

注意没有5-HT1C受体。这是因为在克隆这个受体并进一步分类之后，发现它和5-HT2家族共同点更多，于是就改名成了5-HT2C受体。

对各5-HT受体亚型选择性极弱的激动剂有麦角胺（一种antimigraine，激活5-HT1A、5-HT1D、5-HT1B、D2、去甲肾上腺素受体[28]）、LSD（一种迷幻药物，激活5-HT1A、5-HT2A、5-HT2C、5-HT5A、5-HT5、5-HT6）。[28]

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外部链接
  • MeSH（醫學主題詞）上面的Serotonin+Receptors（美式英语）
  • . IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. （原始内容存档于2016-06-01）.
  • Rubenstein, LA, Lanzara RG. . Cogprints. 2005-02-16 [2008-04-11]. （原始内容存档于2011-05-16）.

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