NEURAL CONTROL OF LARGE INTESTINAL MUCOSA

大肠粘膜的神经控制

• 批准号: 2634205
• 负责人: HELEN J COOKE
• 金额: $ 21.3万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2634205
• 关键词: autonomic reflex; chloride ion; colon; diarrhea; electrophysiology; gastrointestinal absorption /transport; gastrointestinal hormones; guinea pigs; histamine; immunocytochemistry; inflammation; intestinal mucosa; ion transport; mast cell; neuroendocrine system; neuroimmunomodulation; neuropeptide receptor; neuroregulation; neurotransmitter transport; prostaglandin receptor; prostaglandins; receptor binding; serotonin receptor; substance P

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.

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。 物质 P 其中 发现在外在和内在神经元中随其升高 炎症期间的受体。 总体目标是确定角色 P物质在神经反射通路中调节上皮功能 豚鼠的结肠。 第一个目标是解决神经分泌是否 由粘膜抚摸和 5-HT1P 受体激活引发的反射 存在于内在传入神经元上刺激氯离子分泌。 粘膜下层/粘膜制剂将被放置在通量室中用于记录 反映离子传输的短路电流（Isc）。 研究会 确定 P 物质是否在反射过程中介导 Isc 增加 通过刺激辣椒素抗性神经元来激活。 物质释放 P 和特定拮抗剂的作用将用于确定 与下游胆碱能或血管活性肠道的突触耦合 肽免疫反应性神经元。 第二个目标是确定是否 P 物质通过释放前列腺素介导其对 Isc 的影响。 在这个 阶段，前列腺素或神经激肽受体的拮抗作用将在 与通过放射免疫测定法测量的前列腺素的释放相结合。 第三个目标是解决肥大细胞在介导分泌中的作用 通过比较肥大细胞增生模型中的反射， 旋毛虫模型，β-乳球蛋白致敏几内亚 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 刺激氯离子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以下方法进行检查 逆转录聚合酶链反应和原位杂交。 125 I-Bolton Hunter 将进行 P 物质结合以验证其存在 神经激肽受体蛋白。 克隆神经激肽受体基因 豚鼠上皮细胞及其在上皮细胞中的表达 线将允许研究它们的功能。 总的来说，这些研究是 预计将为神经反射途径提供重要的见解 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有 P 物质的神经元 炎症。