Serotonin and neuroprotection in functional bowel disorders
Serotonin and neuroprotection in functional bowel disorders
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DOI：
10.1111/j.1365-2982.2007.00962.x
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发表时间：
2007-08-01
影响因子：
3.5
通讯作者：
Liu, M.-T.
中科院分区：
文献类型：
--
作者：
Gershon, M. D.;Liu, M.-T.
5-HT 4部分激动剂替加色罗对慢性便秘和便秘型肠易激综合征有较好的治疗作用。5-HT 4受体位于肠神经系统中的突触前末梢上。5-HT 4受体的刺激增强了乙酰胆碱和降钙素基因相关肽从受刺激的神经末梢的释放。这一行动加强了促动力途径中的神经传递，增强了胃肠动力。在小鼠中敲除5-HT 4受体不仅减缓了胃肠活动，而且在1个月大后，增加了与年龄相关的肠神经元损失，并减少了存活神经元的大小。5-HT 4受体激动剂，替加色罗和RS67506，增加肠神经元从前体细胞发育和/或在培养物中存活的数量;它们还增加神经突生长并减少细胞凋亡。5-HT 4受体拮抗剂GR 113808阻断所有这些作用，因此这些作用是特异性的和5-HT 4介导的。因此，5-HT 4受体激动剂对肠神经元具有神经保护和神经营养作用。由于年龄相关的肠神经元数量下降可能导致老年人的运动障碍，因此应研究5-HT激动剂的神经保护作用是否可用于预防这些疾病的发生或恶化。
The 5-HT4 partial agonist tegaserod is effective in the treatment of chronic constipation and constipation predominant irritable bowel syndrome. 5-HT4 receptors are located on presynaptic terminals in the enteric nervous system. Stimulation of 5-HT4 receptors enhances the release of acetylcholine and calcitonin gene related peptide from stimulated nerve terminals. This action strengthens neurotransmission in prokinetic pathways, enhancing gastrointestinal motility. The knockout of 5-HT4 receptors in mice not only slows gastrointestinal activity but also, after 1 month of age, increases the age-related loss of enteric neurons and decreases the size of neurons that survive. 5-HT4 receptor agonists, tegaserod and RS67506, increase numbers of enteric neurons developing from precursor cells and/or surviving in culture; they also increase neurite outgrowth and decrease apoptosis. The 5-HT4 receptor antagonist, GR113808, blocks all of these effects, which are thus specific and 5-HT4-mediated. 5-HT4 receptor agonists, therefore, are neuroprotective and neurotrophic for enteric neurons. Because the age-related decline in numbers of enteric neurons may contribute to the dysmotilities of the elderly, the possibility that the neuroprotective actions of 5-HT agonists can be utilized to prevent the occurrence or worsening of these conditions should be investigated.