Peripheral neural serotonin receptors: identification and characterization with specific antagonists and agonists.
Peripheral neural serotonin receptors: identification and characterization with specific antagonists and agonists.
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外周神经血清素受体：特定拮抗剂和激动剂的鉴定和表征。
DOI：
10.1073/pnas.83.24.9799
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发表时间：
1986
影响因子：
11.1
通讯作者：
Gershon,MD
中科院分区：
文献类型：
--
作者：
Mawe,GM;Branchek,TA;Gershon,MD
血清素（5-羟色胺，5-HT）已被证明是肠神经系统（ENS）中的一种神经递质。尽管 5-HT 是神经节间结缔组织刺激引起的缓慢兴奋性突触后电位的介体，但其在肠道生理学中所起的确切作用尚不清楚。由于对 ENS 中 5-HT 受体类型了解不足，因此缺乏特征明确的拮抗剂，研究受到阻碍。我们现在报道了两类肠神经 5-HT 受体的鉴定、激活这些受体对肌间 II/AH 型神经元的影响，以及它们与特定激动剂和拮抗剂的表征。我们建议将其中一类称为 5-HT1P，其特点是在放射性配体结合测定中对 [3H]5-HT 具有高亲和力。此类受体介导与输入阻力增加相关的肌间 II/AH 型神经元的缓慢去极化。除 5-HT（按效力顺序）外，该受体的激动剂还包括 5- 和 6-羟基吲哚平以及 2-甲基-5-HT。 5-HT1P 介导的反应可被 5-羟色氨酸-5-羟色氨酸酰胺特异性拮抗。另一类 5-HT 受体，我们建议将其称为 5-HT2P，似乎对 [3H]5-HT 没有高亲和力。该受体介导与输入电阻下降相关的肌间 II/AH 神经元的短暂去极化。低浓度的 2-Mmethyl-5-HT 是该受体的特异性激动剂，ICS 205-930 是该受体的特异性拮抗剂。 [3H]5-HT 与肠膜的结合可被 5-HT1P 受体激动剂和拮抗剂抑制，但不会被 5-HT2P 受体拮抗剂 ICS 205-930 或 MDL 72222 抑制，MDL 72222 是另一种据报道是外周受体 5-HT 拮抗剂的化合物。
Serotonin (5-hydroxytryptamine, 5-HT) has been shown to be a neurotransmitter in the enteric nervous system (ENS). Although 5-HT is a mediator of slow excitatory postsynaptic potentials evoked by stimulation of interganglionic connectives, the precise role it plays in the physiology of the gut is unclear. Research has been hampered by an inadequate knowledge of the types of 5-HT receptor in the ENS and thus the lack of well-characterized antagonists. We now report the identification of two classes of enteric neural 5-HT receptor, the effects of activating these receptors on myenteric type II/AH neurons, and their characterization with specific agonists and antagonists. One class, which we propose to call 5-HT1P, is characterized by a high affinity for [3H]5-HT in radioligand binding assays. This class of receptor mediates a slow depolarization of myenteric type II/AH neurons associated with an increase in input resistance. Agonists at this receptor include, in addition to 5-HT (in order of potency), 5- and 6-hydroxyindalpine and 2-methyl-5-HT. 5-HT1P-mediated responses are specifically antagonized by 5-hydroxytryptophyl-5-hydroxytryptophan amide. The other class of 5-HT receptor, which we propose to call 5-HT2P, appears not to have a high affinity for [3H]5-HT. This receptor mediates a brief depolarization of myenteric II/AH neurons associated with a fall in input resistance. 2-Methyl-5-HT, at low concentrations, is a specific agonist at this receptor and ICS 205-930 is a specific antagonist. Binding of [3H]5-HT to enteric membranes is inhibited by 5-HT1P receptor agonists and antagonists but not by the 5-HT2P receptor antagonist ICS 205-930 or by MDL 72222, another compound reported to be an antagonist of 5-HT at peripheral receptors.