A dual role of 5-hydroxytryptamine receptor 3 in serotonin induced ion transport in rat distal colon.
A dual role of 5-hydroxytryptamine receptor 3 in serotonin induced ion transport in rat distal colon.
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DOI：
10.1016/j.ejphar.2008.01.027
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发表时间：
2008-04
影响因子：
5
通讯作者：
N. Yang;Yue-Min Tian;Xiao-Hui Zhang;L. Zheng;H. Xue;Xin Chen;Lin Zhu;Jin-Xia Zhu
中科院分区：
文献类型：
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作者：
N. Yang;Yue-Min Tian;Xiao-Hui Zhang;L. Zheng;H. Xue;Xin Chen;Lin Zhu;Jin-Xia Zhu
5-羟色胺（5-HT）诱导的小肠分泌可分为神经途径和非神经途径。近年来，神经通路中的5-HT 3受体作为肠道疾病的可能靶点受到了广泛关注。本研究旨在利用大鼠完整结肠和粘膜/粘膜下层标本，研究不同肠神经丛（肌间神经丛和粘膜下神经丛）5-HT 3受体对大鼠结肠离子转运的影响。本研究采用了Ussing小室和实时荧光PCR技术。令人惊讶的是，我们发现在粘膜/粘膜下层制备物中，5-HT诱导的ΔISC（短路电流的变化）不受抑制，但通过5-HT 3受体拮抗剂MDL 72222和托潘基-3，5-二甲基苯甲酸酯预处理进一步增加。河豚毒素（TTX）的存在下，这种反应显着减弱。相反，在大鼠完整结肠中，5-HT 3受体拮抗剂显著抑制5-HT诱导的ΔISC。实时荧光定量PCR结果证实5-HT 3受体存在于外肌层和粘膜下层。因此，5-HT 3受体对大鼠远端结肠电解质分泌、肌间神经丛5-HT 3受体的神经刺激作用和粘膜下神经丛5-HT 3受体的抑制作用具有双重调节作用。
5-hydroxytryptamine (5-HT)-evoked intestinal secretion can be divided into neural and non-neural pathway. Recently, 5-HT3receptor in neural pathway received much attention as a possible target in bowel diseases. The present study aims to investigate the effects of 5-HT3receptor in different enteric neural plexus (myenteric plexus and submucosal plexus) on rat colonic ion transport by using rat intact colon and mucosa/submucosa preparations. Ussing chamber and real-time PCR techniques were performed in our present study. Surprisingly, we found that in mucosa/submucosa preparations, 5-HT-induced ΔISC(change in short-circuit current) was not inhibited, but further increased by pretreatment with 5-HT3receptor antagonists, MDL72222 and Tropanyl-3, 5-dimethylbenzoate. And this response was significantly attenuated in the presence of tetrodotoxin (TTX). Conversely, in rat intact colon, 5-HT3receptor antagonists significantly inhibited 5-HT-induced ΔISC. The results from real-time PCR proved the existence of 5-HT3receptor in muscularis externa and submucosa. Taken together, 5-HT3receptors possess a role of dual regulation on electrolyte secretion in rat distal colon, the neural stimulatory effect of 5-HT3receptor in myenteric plexus and the inhibitory effect of 5-HT3receptor in submucosal plexus.