Trafficking of Receptors and Receptor Associated Proteins in Enteric Neurons and their Effectors

食物通过消化道的移动和消化是由嵌入胃壁和肠壁的肠道神经系统控制的。肠道神经系统的神经元含有并释放起神经递质作用的化学物质，将信息从一个神经元传递到另一个神经元。神经功能异常可能导致肠道敏感性增加(疼痛)，内容物反向移动(反流)，或无法移动内容物(停滞)，导致消化不良。许多参与神经元之间传递的化学物质已经被识别出来。另一个重要的问题是：在由许多神经元组成的通路中，每种化学物质在哪里释放，它在哪里发挥作用？我们正在使用荧光标签、共聚焦显微镜和计算机成像技术来查看神经元内的化学物质。我们还能够看到递质与(它们的受体)结合的分子，以及当化学信使结合时这些受体发生的变化。我们可以观察肠道内的神经元，并确定接收特定化学信息的单个神经元。我们正在确定由乙酰胆碱(引起神经元兴奋和肌肉收缩的主要递质)、速激肽(参与收缩、放松和疼痛途径的多肽)以及其他涉及收缩、松弛和分泌的递质(血管活性肠肽、生长抑素、胃泌素释放肽、胆囊收缩素和胃动素)激活的神经元的位置。这项研究的结果将为涉及神经递质正常释放或其受体激活变化的疾病的治疗提供合理的基础。

Movement of food through the alimentary tract and digestion of that food are controlled by the enteric nervous system which is embedded in the walls of the stomach and intestines. The neurons of the enteric nervous system contain and release chemicals that act as neurotransmitters, passing messages from one neuron to the next. Abnormalities of neuronal function can result in increased sensitivity (pain) from the gut, contents moving in reverse (reflux), or failure to move contents (stasis) resulting in maldigestion. Many of the chemicals involved in transmission between neurons have been identified. An important further question is: where, in a pathway consisting of many neurons, is each chemical released and where does it have its effect? We are using techniques to see the chemicals within the neurons using fluorescent tags, confocal microscopy and computer imaging. We are also able to see the molecules that the transmitters bind to (their receptors) and to see changes in these receptors that occur when the chemical messenger binds. We can look at the neurons within the intestine and determine the individual neurons that receive a particular chemical message. We are determining the location of neurons that are activated by acetylcholine (the major transmitter causing excitation of neurons and contraction of the muscle), tachykinins (peptides involved in pathways of contraction, relaxation and pain) and other transmitters (vasoactive intestinal peptide, somatostatin, gastrin releasing peptide, cholecystokinin and motilin) involved in contraction, relaxation and secretion. The results of this study will provide a rational basis for therapeutic treatment of disorders that involve changes in the normal release of neurotransmitters or changes in the activation of their receptors.