Intestinal serotonin acts as paracrine substance to mediate pancreatic secretion stimulated by luminal factors.
Intestinal serotonin acts as paracrine substance to mediate pancreatic secretion stimulated by luminal factors.
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DOI：
10.1152/ajpgi.2001.281.4.g916
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发表时间：
2001-10
期刊：
影响因子：
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通讯作者：
Y. Li;X. Y. Wu;J. X. Zhu;C. Owyang
中科院分区：
文献类型：
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作者：
Y. Li;X. Y. Wu;J. X. Zhu;C. Owyang
我们最近证明，管腔因素，如渗透压，双糖，和机械刺激引起胰腺分泌激活5-羟色胺亚型3（5-羟色胺-3，5-HT 3）受体的粘膜迷走神经传入纤维在肠道。我们假设腔刺激释放的5-HT作为旁分泌物质，激活粘膜迷走神经传入纤维以刺激胰腺分泌。在体内大鼠模型中，麦芽糖或高渗NaCl的管腔灌注使肠流出液灌注液中5-HT水平增加三倍。在管腔内灌注10（-5）M 5-HT后观察到类似的水平。这些治疗不会影响5-HT血液水平。在另一项研究中，十二指肠内（而非回肠内）应用5-HT可诱导胰腺蛋白分泌呈剂量依赖性增加，CCK-A拮抗剂CR-1409并未阻止这种增加。急性迷走神经切断术，甲基东莨菪碱，或迷走神经周围或肠粘膜应用辣椒素废除5-HT诱导的胰腺分泌。在清醒大鼠中，鲁米那10（-5）M 5-HT给药可使胰腺蛋白输出增加90%，而5-HT 3拮抗剂昂丹司琼可显著抑制这种增加。总之，腔刺激诱导5-HT释放，这反过来又激活5-HT 3受体上的粘膜迷走神经传入末梢。以这种方式，5-HT作为旁分泌物质通过迷走胆碱能途径刺激胰腺分泌。
We recently demonstrated that luminal factors such as osmolality, disaccharides, and mechanical stimulation evoke pancreatic secretion by activating 5-hydroxytryptamine subtype 3 (serotonin-3, 5-HT3) receptors on mucosal vagal afferent fibers in the intestine. We hypothesized that 5-HT released by luminal stimuli acts as a paracrine substance, activating the mucosal vagal afferent fibers to stimulate pancreatic secretion. In the in vivo rat model, luminal perfusion of maltose or hypertonic NaCl increased 5-HT level threefold in intestinal effluent perfusates. Similar levels were observed after intraluminal 10(-5) M 5-HT perfusion. These treatments did not affect 5-HT blood levels. In a separate study, intraduodenal, but not intraileal, 5-HT application induced a dose-dependent increase in pancreatic protein secretion, which was not blocked by the CCK-A antagonist CR-1409. Acute vagotomy, methscopolamine, or perivagal or intestinal mucosal application of capsaicin abolished 5-HT-induced pancreatic secretion. In conscious rats, luminal 10(-5) M 5-HT administration produced a 90% increase in pancreatic protein output, which was markedly inhibited by the 5-HT3 antagonist ondansetron. In conclusion, luminal stimuli induce 5-HT release, which in turn activates 5-HT3 receptors on mucosal vagal afferent terminals. In this manner, 5-HT acts as a paracrine substance to stimulate pancreatic secretion via a vagal cholinergic pathway.