ETHANOL MODULATION OF ENTERIC NEUROTRANSMISSION

描述：（改编自研究者摘要）高或慢性 酒精摄入，胃肠（GI）道运动障碍， 特别常见，包括食道蠕动减少、食道 反流、胃排空异常、肠功能亢进和腹泻。 虽然 通常认为乙醇（EtOH）直接作用于GI平滑肌， P.I.的初步研究表明，一个更敏感的目标是 肠神经系统（ENS）位于肠壁内。 ENS协调 食糜在整个胃肠道中的推进（消化）。 从他们 在豚鼠回肠的初步研究中，研究人员发现， EtOH增强肠兴奋性反射和低血糖 浓度（0.001至0.2% v/v），通过明显增加胆碱能和 非胆碱能神经传递，而乙醇在较高浓度 （> 0.5%v/v），抑制肠兴奋性反射和痉挛， 对肌间神经元的突触后作用。 根据这些观察， 本研究的长期目的是确定急性乙醇对 神经传递的豚鼠回肠在体外。 豚鼠回肠是 一个很好的模型，这些研究作为一个层次结构的强大和 针对这种组织已经开发了敏感技术， EtOH对肠道神经传递的影响将在许多方面进行研究， 水平，范围从孤立的回肠段中的肿胀到 单个肌间神经元的水平。 特别是，P.I.将研究 EtOH的作用; i）兴奋，ii）特定的上行兴奋 以及下行的抑制性神经通路， 肠神经元的反射反应，位于特定的 神经通路;以及iv）膜特性和突触输入（快速和快速）。 慢）的特点肌间神经元。 由于EtOH可以通过以下方式影响肠道 直接作用于粘膜，他们还将测试v）EtOH是否可以影响 通过直接刺激内在感觉神经末梢， 粘膜绒毛，和vi）确定EtOH是否直接或间接作用于 通过释放神经调节剂如一氧化氮， 5-羟色胺、阿片类、腺苷或肾上腺素。 本研究将提供 对EtOH如何影响肠道神经传递的重要见解， 改变肠道蠕动

DESCRIPTION: (Adapted from Investigator's Abstract) After high or chronic alcohol intake, motility disorders of the gastrointestinal (GI) tract are particularly common, including decreased esophageal peristalsis, esophageal reflux, abnormal gastric emptying, hyperactive bowel and diarrhea. Although ethanol (EtOH) is generally assumed to act directly on GI smooth muscle, the P.I.'s preliminary studies suggest that a more sensitive target is the enteric nervous system (ENS) within the gut wall. The ENS coordinates the propulsion (peristalsis) of chyme throughout the GI tract. From their preliminary studies in the guinea-pig ileum the investigators have found EtOH to enhance enteric excitatory reflexes and peristalsis at low concentrations (0.001 to 0.2% v/v) by apparently increasing cholinergic and non-cholinergic neurotransmission, whereas, EtOH at higher concentrations (>0.5 % v/v), depresses both enteric excitatory reflexes and peristalsis by postsynaptic actions on myenteric neurons. In light of these observations, the long term aim of this study is to determine the actions of acute EtOH on neurotransmission in the guinea-pig ileum in-vitro. The guinea-pig ileum is an excellent model for these studies as a hierarchy of powerful and sensitive techniques have been developed for this tissue that will enable the effects of EtOH on enteric neurotransmission to be investigated at many levels, ranging from peristalsis in isolated segments of ileum down to the level of individual myenteric neurons. In particular, the P.I. will study the actions of EtOH on; i) peristalsis, ii) specific ascending excitatory and descending inhibitory nerve pathways to muscles that underlie peristalsis; iii) reflex responses in enteric neurons located in specific nerve pathways; and iv) membrane properties and synaptic inputs (fast and slow) of characterized myenteric neurons. As EtOH can effect the gut by direct actions on the mucosa, they will also test v) whether EtOH can effect peristalsis by directly stimulating intrinsic sensory nerve endings in mucosal villi, and vi) determine whether EtOH acts directly or indirectly on neural excitability by releasing neuromodulators such as nitric oxide, serotonin, opiodes, adenosine or prostaglandins. This study will provide significant insights into how EtOH affects enteric neurotransmission to alter gut motility.