SPINAL AND BRAIN MODULATION OF GASTROINTESTINAL MOTILITY

最近发现，中枢神经系统（CNS）发挥 对胃肠道（GI）运动的重要调节作用。 CNS 神经肽似乎在中枢调节中特别重要， 能动性 某些集中分布的“脑肠”神经肽 外源性给药对运动和反射有显著影响 的胃肠道。 具体的网站或机制，通过这些 肽对肠道的影响尚未确定。 神经肽可以作用于 影响胃肠道运动功能的4个独立部位：大脑、 肠神经系统，肠道平滑肌，而且，只有非常 最近被证实的脊髓 这是一个假设 “脑-肠”肽通过化学敏感位点起作用， 脑和脊髓作为生理或药理学 胃肠道运动的调节剂。 我们建议把研究的重点放在 哺乳动物蛙皮素（胃泌素释放肽; GRP）、促甲状腺激素 释放激素和某些阿片类神经肽（a）持续和（B） 引起了肠道的反射活动。 我们的方法最初将涉及 将神经肽施用到脑中和脊髓中 蛛网膜下腔从根本上确定化学敏感部位 参与控制胃肠道运动。 待研究的终点为 我们实验室的所有标准品，包括胃 排空和小肠和大肠运输，胃和肠 大鼠的管腔内压力以及小鼠的GI通过。 在 此外，最近开发的模型提出的研究是诱发的 大鼠胃结肠反射。 将采用的主要技术 剖析控制肠道的肽能途径包括：（a） 向特定脑位置和脊髓水平进行显微注射，和（B） 在不同水平横断脊髓， 可以确定交感神经或副交感神经肠神经支配。 我们 最近的工作提供了证据表明，脊髓中的肽敏感位点 脊髓可从解剖学、解剖学和功能上加以区分 大脑中的那些。 对网站和功能的了解 神经元“脑肠”肽将提供关于中枢神经系统的新信息。 神经系统与肠道的相互作用

It is recently evident that the central nervous system (CNS) exerts important regulatory influences on gastrointestinal (GI) motility. CNS neuropeptides appera to be especially important in central regulation of motility. Certain of the centrally-distributed "brain-gut" neuropeptides administered exogenously have dramatic effects on the motility and reflexes of the GI tract. The specific sites or mechanisms through which these peptides affect the gut have not been determined. Neuropeptides can act at 4 discrete sites in affecting GI motor function: the brain, the neurons of the enteric nervous system, the smooth muscle of the gut, and, as only very recently demonstrated, the spinal cord. It is the hypothesis of this proposal that the "brain-gut" peptides act through chemosensitive sites in the brain and spinal cord to serve as physiological or pharmacological modulators of GI motility. We propose to focus our studies on the central effects of mammalian bombesin (gastrin releasing peptide; GRP), thyrotropin releasing hormone and certain opioid neuropeptides on (a) ongoing and (b) evoked reflex activity of the gut. Our approach will initially involve administration of neuropeptides into the brain and into the spinal subarachnoid space to define the chemosensitive sites fundamentally involved in the control of GI motility. The endpoints to be studied are all standard in our laboratory and include determination of gastric emptying and small and large bowel transit, stomach and intestinal intraluminal pressure in the rat as well as GI transit in the mouse. In addition, a recently developed model proposed for study is the evoked gastrocolic reflex in the rat. The major techniques that will be employed to dissect the peptidergic pathways that control the gut include: (a) microinjections into specific brain locations and cord levels and (b) transection of the spinal cord at various levels so that the influence of the sympathetic or parasympathetic gut innervation can be determined. Our recent work provides evidence that peptide sensitive sites in the spinal cord can be distinguished anatomically, pharmacologically and functionally from those in the brain. Knowledge of the sites and functions of the neuronal "brain-gut" peptides will provide new information about central nervous system-gut interactions.