Analysis of the role of 5-HT in the enteric nervous system using anti-idiotopic antibodies to 5-HT receptors.

Analysis of the role of 5-HT in the enteric nervous system using anti-idiotopic antibodies to 5-HT receptors.
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使用 5-HT 受体抗独特位抗体分析 5-HT 在肠神经系统中的作用。

DOI:
10.1152/ajpgi.1994.266.3.g403
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发表时间:
1994
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Gershon,MD
Gershon,MD
中科院分区:
--
文献类型:
--
作者:
Wade,PR;Tamir,H;Kirchgessner,AL;Gershon,MD

文献摘要

被引文献

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用电生理学方法研究了识别5-羟色胺(5-HT)受体的抗独特型抗体(α-id)对豚鼠小肠肌间神经元的作用,并用免疫细胞化学方法定位了α-id结合位点。α-id的初始应用模拟了5-HT的三种作用中的每一种:快速去极化,与输入电阻(Rin)的下降相关,其被5-HT 3拮抗剂托烷司琼抑制(≥ 1 μ M)和伦扎必利(100微M);缓慢的膜去极化,与Rin增加相关,5-HT 1 P拮抗剂伦扎必利可抑制该作用,但5-HT 4阻断浓度的托烷司琼不影响该作用(10微M);和超极化,与Rin降低,这是拮抗5-HT 1A抑制剂NAN-190。交叉脱敏反应之间观察到5-HT和alpha-id。暴露于alpha-id后,随后的反应alpha-id,5-HT,和刺激诱发的慢兴奋性突触后电位被拮抗,但卡巴胆碱和P物质的反应不受影响。因此,α-id特异性抑制内源性释放和外源性应用的5-HT的作用。α-id结合到肌间和粘膜下神经元和上皮下神经丛上的位点。α-id的结合被5-HT 1 P-、5-HT 3-和5-HT 4-特异性拮抗剂阻断。我们的结论是,α-id选择性地结合所有已知亚型的5-HT受体在肠神经系统,因此是有用的研究胃肠功能的5-HT。
The effects of anti-idiotypic antibodies (alpha-id) that recognize serotonin [5-hydroxytryptamine (5-HT)] receptors on myenteric neurons of the guinea pig small intestine were characterized electrophysiologically, and alpha-id binding sites were located immunocytochemically. Initial applications of the alpha-id mimicked each of three actions of 5-HT: a rapid depolarization, associated with a fall in input resistance (Rin), which was inhibited by the 5-HT3 antagonists tropisetron (> or = 1 microM) and renzapride (100 microM); a slow membrane depolarization, associated with increased Rin, that was inhibited by the 5-HT1P antagonist renzapride but was unaffected by a 5-HT4 blocking concentration of tropisetron (10 microM); and a hyperpolarization, associated with decreased Rin, that was antagonized by the 5-HT1A inhibitor NAN-190. Cross-desensitization was observed between responses to 5-HT and the alpha-id. After exposure to the alpha-id, subsequent responses to the alpha-id, 5-HT, and stimulus-evoked slow excitatory postsynaptic potentials were antagonized; however, responses to carbachol and substance P were unaffected. The alpha-id thus specifically inhibits the effects of endogenously released and exogenously applied 5-HT. The alpha-id bound to sites on myenteric and submucosal neurons and a subepithelial nerve plexus. Binding of the alpha-id was blocked by 5-HT1P-, 5-HT3-, and 5-HT4-specific antagonists. We concluded that the alpha-id binds selectively to all known subtypes of 5-HT receptor in the enteric nervous system and is thus useful for investigating the gastrointestinal function of 5-HT.