SPINAL & BRAIN MODULATION OF GASTROINTESTINAL MOTILITY

最近有证据表明，中枢神经系统(CNS) 对胃肠(GI)运动的重要调节影响。 中枢神经系统神经肽似乎在中枢神经系统中尤为重要 对运动的调节。某些集中分布的 外源性“脑-肠”神经肽有戏剧性的作用 对胃肠道运动和反射的影响。具体的 这些多肽影响肠道的部位或机制 还没有确定。神经肽可以以离散的方式发挥作用 影响胃肠道运动功能的部位：大脑、 肠道神经系统，肠道的平滑肌肉，作为唯一的 最近展示的是脊髓。这是一种假设 “脑-肠道”多肽通过 大脑和脊髓中的化学敏感部位作为 胃肠动力的生理或药物调节剂。我们 建议将我们的研究重点放在哺乳动物的中枢作用上 蛙皮素胃泌素释放肽(GRP)，促肾上腺皮质激素释放 激素(CRF)和某些阿片类神经肽(A)正在进行和 (B)引起肠道反射活动。我们的方法最初将 涉及到神经肽进入大脑和进入 脊髓蛛网膜下腔对化疗敏感部位的定位 从根本上参与控制胃肠动力。这个 要研究的终端都是我们实验室的标准配置， 包括测定胃排空、小肠和大肠 大鼠运输、胃和肠腔内压力的研究 就像GI在老鼠里穿梭一样。此外，最近的一次 建议研究的发展模型是诱发的胃结肠反射。 在老鼠身上。将用于解剖的主要技术 控制肠道的多肽能途径包括：(A) 在特定的脑位置和脊髓水平进行微量注射 (B)在不同水平横断脊髓，使 交感神经或副交感神经对肠道神经的影响 要下定决心。我们最近的研究提供了多肽的证据 可以区分脊髓中的敏感部位 在解剖学上、药理学上和功能上与那些 大脑。关于神经元的位置和功能的知识 “脑-肠”多肽将提供有关中枢的新信息 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.