ETHANOL MODULATION OF ENTERIC NEUROTRANSMISSION

描述：(改编自《调查者摘要》)在高或慢之后 酒精摄入，胃肠道动力障碍 尤其常见，包括食道蠕动减弱，食道 反流、胃排空异常、大便亢进和腹泻。虽然 乙醇(Etoh)通常被认为直接作用于胃肠道平滑肌， S的初步研究表明，更敏感的目标是 肠壁内的肠道神经系统(ENS)。ENS协调 整个胃肠道食管壁的推进(蠕动)。从他们的 研究人员在豚鼠回肠中发现了初步研究 乙醇增强低位时的肠道兴奋性反射和蠕动 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，而高浓度的乙醇 (&gt；0.5%v/v)，通过抑制肠道兴奋性反射和蠕动 突触后对肌间神经元的作用。根据这些观察结果， 这项研究的长期目标是确定急性无水乙醇对 豚鼠回肠神经传递的体外研究。豚鼠回肠是 这些研究的一个极好的模型，作为一个强大的和 已经为这种组织开发了敏感的技术，这将使 乙醇对肠道神经传递的影响有待多方面研究 水平，从孤立的回肠段的蠕动到 单个肌间神经元的水平。特别是，私家侦探将研究 乙醇在以下方面的作用：i)蠕动，ii)特异性上行兴奋 以及下行抑制神经通路到肌肉的基础 蠕动；iii)位于特定位置的肠神经细胞的反射反应 神经通路；以及iv)膜特性和突触输入(快速和 慢)特征的肌间神经元。因为乙醇可以通过以下方式影响肠道 对粘膜的直接作用，他们也会测试v)乙醇是否能影响 直接刺激内源性感觉神经末梢引起的蠕动 粘膜绒毛，和vi)决定乙醇是否直接或间接作用于 神经兴奋性通过释放神经调节剂，如一氧化氮， 5-羟色胺、阿片、腺苷或前列腺素。这项研究将提供 乙醇如何影响肠道神经传递的重要见解 改变肠道动力。

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.