IDENTIFICATION AND DISTRIBUTION OF 5-HT3 RECEPTORS IN RAT-BRAIN USING RADIOLIGAND BINDING
IDENTIFICATION AND DISTRIBUTION OF 5-HT3 RECEPTORS IN RAT-BRAIN USING RADIOLIGAND BINDING
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DOI：
10.1038/330746a0
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发表时间：
1987-12-24
期刊：
影响因子：
64.8
通讯作者：
TYERS, MB
中科院分区：
文献类型：
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作者：
KILPATRICK, GJ;JONES, BJ;TYERS, MB
5-羟色胺（5-hydroxytryptamine，5-HT）受体分为3种亚型：5-HT 1、5-HT 2和5-HT 3。5-HT 1和5-HT 2亚型的脑结合位点已被确定。5-HT 3型受体已在离体外周组织模型（如大鼠迷走神经2、豚鼠回肠3和离体兔心脏4）上进行了表征。利用这些模型，已经开发出选择性5-HT 3受体拮抗剂，如MDL 72222（参考文献5）、ICS 205-930（参考文献6）、GR 38032 F（参考文献7）和BRL 43694（参考文献8）。最近，GR 38032 F、MDL 72222和ICS 205-930已被证明在啮齿动物和灵长类动物中具有行为效应，这无疑反映了中枢神经系统的作用（参考文献9-11和未发表的观察结果），表明大脑中存在5-HT 3受体。本文报道了5-HT_3受体拮抗剂3 H-GR_（65630）与大鼠内嗅皮质匀浆的高亲和力结合，为5-HT_3受体在大鼠脑组织中的存在及其分布提供了直接证据。选择性5-HT 3受体拮抗剂和激动剂以高亲和力抑制3 H-GR 65630的结合，这与它们对大鼠离体迷走神经的作用密切相关2。结合在整个大脑中分布差异，在皮质和边缘区浓度较高。
Functional serotonin (5-hydroxytryptamine, 5-HT) receptors have been divided into three subtypes: 5-HT1,-like, 5-HT2and 5-HT3, (ref. 1). Brain binding sites have been identified for both the 5-HT1, and 5-HT2subtypes. Receptors of the 5-HT3type have been characterized on isolated peripheral tissue models such as the rat vagus nerve2, guinea-pig ileum3and isolated rabbit heart4. Using these models, selective 5-HT3receptor antagonists such as MDL 72222 (ref. 5), ICS 205-930 (ref. 6), GR38032F (ref. 7) and BRL 43694 (ref. 8) have been developed. Recently, GR38032F, MDL 72222 and ICS 205-930 have been shown to have behavioural effects in rodents and primates that undoubtedly reflect an action in the central nervous system (refs 9–11 and unpublished observations), suggesting the existence of 5-HT3receptors in the brain. Here we report direct evidence for the existence of 5-HT3receptors in rat brain tissue and their distribution, based on high affinity binding of the potent 5-HT3receptor antagonist3H-GR65630 to homogenates of rat entorhinal cortex. Selective 5-HT3receptor antagonists and agonists inhibited binding of3H-GR65630 with high affinities which correlated well with their actions on the rat isolated vagus nerve2. Binding was differentially distributed throughout the brain with high concentrations in cortical and limbic areas.