NEURAL CONTROL OF LARGE INTESTINAL MUCOSA

描述：腹泻是炎症最常见的症状之一， 肠道疾病寄生虫感染和食物过敏 P物质， 在外源性和内源性神经元中发现， 炎症过程中的受体。 总体目标是确定以下方面的作用： P物质在调节上皮功能神经反射通路中的作用 豚鼠的结肠 第一个目标是解决神经分泌是否 粘膜刺激和5-HT 1 P受体激活触发的反射 刺激氯化物分泌。 将粘膜下层/粘膜制备物置于通量室中进行记录 短路电流（Isc）反映离子迁移。 研究将 确定P物质是否介导反射过程中Isc的增加 通过刺激辣椒素抗性神经元激活。 物质释放 P和特异性拮抗剂的作用将被用来确定 与下游胆碱能或血管活性肠神经元的突触偶联 肽免疫反应神经元。 第二个目标是确定是否 P物质通过释放β-肾上腺素介导其对Isc的作用。 在这 阶段，将检查前列腺素或神经激肽受体的拮抗作用， 与释放的甘草素结合，通过放射免疫测定法测量。 第三个目的是阐述肥大细胞在介导分泌性 通过比较肥大细胞增生模型中的反射， 旋毛虫模型，使用β-乳球蛋白致敏的豚鼠 肥大细胞数量正常的猪模型。 第三个目标是确定 P物质是否激活上皮细胞上的神经激肽受体， 刺激氯分泌和前列腺素合成。 基因表达 神经激肽受体的细胞定位将通过 逆转录-聚合酶链反应和原位杂交。 将进行125 I-Bolton Hunter P物质结合，以验证是否存在 神经激肽受体蛋白。 神经激肽受体基因的克隆 在豚鼠上皮细胞中及其在上皮细胞中的表达 线将允许研究其功能。 总的来说，这些研究 有望为神经反射通路提供重要的见解， 控制肠道内容物的流动性，特别是， 正常或病理生理状态下含P物质神经元的 炎症。

DESCRIPTION: Diarrhea is one of the most common symptoms of inflammatory bowel disease, parasitic infections and food allergies. Substance P which is found in extrinsic and intrinsic neurons is elevated along with its receptor during inflammation. The overall goal is to identify the role of substance P in neural reflex pathways that regulate epithelial function in the colon of guinea pigs. The first aim addresses whether neural secretory reflexes triggered by mucosal stroking and activation of 5-HT1P receptors present on intrinsic afferent neurons stimulate chloride secretion. Submucosa/mucosa preparations would be set up in flux chambers for recording short-circuit current (Isc) which reflects ion transport. Studies would identify whether substance P mediates increases in Isc during reflex activation by stimulating capsaicin-resistant neurons. Release of substance P and the effects of specific antagonists would be used to determine the synaptic coupling to down stream cholinergic or vasoactive intestinal peptide-immunoreactive neurons. The second aim is to determine whether substance P mediates it effects on Isc by releasing prostaglandins. In this phase, antagonism at prostanoid or neurokinin receptors would be examined in conjunction with release of prostaglandins, measured by radioimmunoassay. The third aim addresses the role of mast cells in mediating secretory reflexes by comparing reflexes in a model of mast cell hyperplasia, the Trichinella spiralis model, with the beta-lactoglobulin-sensitized guinea pig model with normal mast cell numbers. The third aim is to determine whether substance P activates neurokinin receptors on epithelial cells to stimulate chloride secretion and prostaglandin synthesis. Gene expression and cellular localization of neurokinin receptors would be examined by reverse transcription-polymerase chain reaction and in situ hybridization. 125 I-Bolton Hunter substance P binding would be done to verify the presence of the neurokinin receptor protein. Cloning the neurokinin receptor genes in guinea pig epithelial cells and their expression in epithelial cells lines would allow study of their function. In general, these studies are expected to provide important insights into the neural reflex pathways that govern the fluidity of the intestinal contents, and in particular, the role of substance P-containing neurons during normal or pathophysiologic states of inflammation.