Gershon M D
Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Curr Opin Gastroenterol. 2000 Mar;16(2):113-20. doi: 10.1097/00001574-200003000-00004.
Alone among organs of the body, the gut is able to mediate reflexes in the absence of input from the brain or spinal cord. This ability appears to be caused by the secretion of serotonin (5-HT) by enterochromaffin (EC) cells of the mucosal epithelium. This 5-HT is secreted into the wall of the gut, where it stimulates the mucosal processes of intrinsic and extrinsic primary afferent neurons. The intrinsic primary afferents, which are activated by 5-HT1P/4 receptors, initiate peristaltic and secretory reflexes. The extrinsic primary afferent neurons send distress and other signals to the central nervous system. Extrinsic nerves are activated by 5-HT(3) receptors. The 5-HT that is involved in mucosal signaling is inactivated by uptake into mucosal epithelial cells, which are mediated by an integral membrane protein called the serotonin reuptake transporter (SERT). The epithelial SERT is the same molecule as that which transports 5-HT in the central and enteric nervous systems. Increasing evidence suggests that abnormal enteric release or inactivation of 5-HT is involved in the pathogenesis of irritable bowel syndrome (IBS). Spread of 5-HT to inappropriate sites in IBS may activate 5-HT(3) receptors on extrinsic afferent fibers and motor neurons, giving rise to visceral hypersensitivity and abnormal motility, respectively. A potent 5-HT(3) antagonist, such as alosetron, can prevent both of these effects and is therefore useful in treating IBS. 5-HT also appears to function as a growth factor in the development of enteric neurons. The developmental effects of 5-HT are mediated by the 5-HT(2B) receptor, which is developmentally regulated. The importance of serotonergic mechanisms in enteric physiology probably accounts for the gastrointestinal "side effects" of compounds that inhibit SERT. The newly discovered role of 5-HT in enteric neuronal development suggests that drugs that interfere with the action or inactivation of 5-HT should be used in pregnancy only with extreme caution, if at all.
在身体的各个器官中，肠道是唯一能够在没有大脑或脊髓输入的情况下介导反射的器官。这种能力似乎是由黏膜上皮的肠嗜铬（EC）细胞分泌血清素（5-羟色胺，5-HT）引起的。这种5-HT分泌到肠壁中，在那里它刺激内在和外在初级传入神经元的黏膜过程。由5-HT1P/4受体激活的内在初级传入神经引发蠕动和分泌反射。外在初级传入神经元将不适和其他信号发送到中枢神经系统。外在神经由5-HT(3)受体激活。参与黏膜信号传导的5-HT通过一种称为血清素再摄取转运体（SERT）的整合膜蛋白介导的摄取作用而失活。上皮SERT与在中枢和肠神经系统中转运5-HT的分子相同。越来越多的证据表明，5-HT在肠道中的异常释放或失活与肠易激综合征（IBS）的发病机制有关。在IBS中，5-HT扩散到不适当的部位可能分别激活外在传入纤维和运动神经元上的5-HT(3)受体，从而导致内脏超敏反应和异常运动。一种有效的5-HT(3)拮抗剂，如阿洛司琼，可以预防这两种效应，因此可用于治疗IBS。5-HT在肠神经元发育过程中似乎也起到生长因子的作用。5-HT的发育效应由发育过程中受调控的5-HT(2B)受体介导。血清素能机制在肠道生理学中的重要性可能解释了抑制SERT的化合物的胃肠道“副作用”。5-HT在肠神经元发育中的新发现作用表明，干扰5-HT作用或失活的药物在孕期应极其谨慎使用，甚至根本不应使用。
