胃肌间神经元亚群通过不同的5-羟色胺受体被差异性激活：投射、神经化学编码及功能意义
Subpopulations of gastric myenteric neurons are differentially activated via distinct serotonin receptors: projection, neurochemical coding, and functional implications.
作者信息
Michel K, Sann H, Schaaf C, Schemann M
机构信息
Physiologisches Institut, Tierärztliche Hochschule, D-30173 Hannover, Germany.
出版信息
J Neurosci. 1997 Oct 15;17(20):8009-17. doi: 10.1523/JNEUROSCI.17-20-08009.1997.
The enteric nervous system coordinates various gut functions. Functional studies suggested that neurotransmitters and neuromodulators, one of the most prominent among them being 5-HT, may act through a specific modulation of ascending and descending enteric pathways. However, it is still mostly unknown how particular components of enteric reflex circuits are controlled. This report describes experiments aimed at identifying a differential activation of enteric pathways by 5-HT. Electrophysiological and immunohistochemical methods were combined to investigate the projection pattern and the transmitter phenotype of 5-HT-sensitive gastric myenteric neurons. Of 294 intracellularly labeled neurons, 60.5% showed responses mediated via 5-HT3 receptors, 11.3% were 5-HT1P-responsive, 3.7% exhibited both 5-HT3 and 5-HT1P receptor-mediated depolarization, and 24.5% were not responding to 5-HT. The 5-HT3-responsive cells were mainly cholinergic (79%) and had ascending projections, whereas the 5-HT1P-responsive cells had primarily descending projections and were nitrergic (67%). Substance P-positive neurons were cholinergic; most of the cells (75%) exhibited 5-HT3 mediated responses and had ascending projections. Muscle strip recordings supported the functional significance of the differential location of 5-HT receptor subtypes. Thus, contractile responses of gastric circular muscle strips were dose-dependently increased by a 5-HT3 and decreased by a 5-HT1P agonist. Results indicated that excitatory ascending enteric pathways consisting of cholinergic, substance Pergic neurons were activated by 5-HT3 receptors, whereas 5-HT1P receptors were involved in activation of inhibitory descending pathways using nitrergic neurons. This suggested that different effects of 5-HT on gastric functions are related to specific activation of receptors located on different subsets of enteric neurons.
肠神经系统协调着肠道的各种功能。功能研究表明，神经递质和神经调质（其中最突出的一种是5-羟色胺）可能通过对肠神经系统上行和下行通路的特定调节发挥作用。然而，肠反射回路的特定组成部分是如何被控制的，目前大多仍不清楚。本报告描述了旨在确定5-羟色胺对肠神经系统通路的差异性激活作用的实验。将电生理和免疫组织化学方法结合起来，研究对5-羟色胺敏感的胃肌间神经元的投射模式和递质表型。在294个经细胞内标记的神经元中，60.5%表现出通过5-羟色胺3型受体介导的反应，11.3%对5-羟色胺1P有反应，3.7%同时表现出5-羟色胺3型和5-羟色胺1P受体介导的去极化，24.5%对5-羟色胺无反应。对5-羟色胺3有反应的细胞主要是胆碱能的（79%），并且有上行投射，而对5-羟色胺1P有反应的细胞主要有下行投射，并且是一氧化氮能的（67%）。P物质阳性神经元是胆碱能的；大多数细胞（75%）表现出5-羟色胺3介导的反应，并且有上行投射。肌条记录支持了5-羟色胺受体亚型不同定位的功能意义。因此，5-羟色胺3型激动剂可使胃环形肌条的收缩反应呈剂量依赖性增加，而5-羟色胺1P激动剂则使其降低。结果表明，由胆碱能、P物质能神经元组成的兴奋性肠神经系统上行通路被5-羟色胺3型受体激活，而5-羟色胺1P受体则参与使用一氧化氮能神经元的抑制性下行通路的激活。这表明5-羟色胺对胃功能的不同作用与位于肠神经元不同亚群上的受体的特异性激活有关。
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