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神经肽似乎在中枢神经系统中特别重要。 运动的调节。 某些集中分布的 外源性给予的“脑肠”神经肽具有显著的 影响胃肠道的运动和反射。 具体 这些肽影响肠道的位点或机制 尚未确定。 神经肽可以在一个离散的 影响胃肠道运动功能的部位：大脑神经元 肠神经系统，肠道平滑肌，以及，作为唯一的 最近才被证实的，脊髓。 这是一个假设 “脑肠”肽通过 大脑和脊髓中的化学敏感部位， 胃肠道运动的生理或药理调节剂。 我们 我建议把我们的研究重点放在哺乳动物的中枢作用上， 蛙皮素促肾上腺皮质激素释放肽 激素（CRF）和某些阿片类神经肽（a）正在进行， (b)引起了肠道的反射活动。 我们的方法将首先 涉及将神经肽施用到大脑和 脊髓蛛网膜下腔以确定化学敏感部位 从根本上参与控制胃肠道运动。 的 待研究的终点均为我们实验室的标准终点， 包括测定胃排空和小肠和大肠 大鼠的通过、胃和肠腔内压力 就像胃肠道在小鼠体内的传输一样。 此外，最近， 提出的研究模型是诱发胃结肠反射 在老鼠。 解剖的主要技术 控制肠道的肽能途径包括：（a） 显微注射到特定的大脑位置和脊髓水平， (b)在不同水平横断脊髓， 交感神经或副交感神经肠神经支配的影响可 下定决心。 我们最近的工作提供了证据， 脊髓中的敏感部位可以被区分 在解剖学上，解剖学上和功能上， 个脑袋 了解神经元的位置和功能 “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 appear to be especially important in central regulation of motility. Certain of the centrally-distributed "brain-gut" neuropeptides administered exogenously have dramatic effects in 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 a 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 agastrin releasing peptide; GRP), corticotropin releasing hormone (CRF) 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 will 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.