CENTRAL NEURAL CONTROL OF GASTRIC MUCOSAL DEFENSE

胃粘膜防御的中枢神经控制

• 批准号: 3237463
• 负责人: GORDON L KAUFFMAN
• 金额: $ 16.12万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3237463
• 关键词: acidity /alkalinity; aminoacid analyzer; antiulcer drug; aspirin; bicarbonates; blood flow measurement; bombesin; calcitonin; calcitonin gene related peptide; central nervous system; centrally acting drug; cerebrospinal fluid; dogs; drug administration routes; drug adverse effect; drug metabolism; endorphins; ethanol; gastric acid; gastric mucosa; gastrointestinal circulation; gastrointestinal pharmacology; laboratory rat; mucus; neural information processing; neuropeptides; neurotensin; peptic ulcer; prostaglandin E; prostaglandin F; prostaglandins; radioimmunoassay; secretion; stomach emptying; thyrotropin releasing hormone; tissue /cell preparation; vagotomy; vasoactive intestinal peptide

These studies are designed to evaluate the role of the central nervous system in gastric mucosal defensive functions, with respect to neuropeptides and prostaglandins. It is hypothesized that 1) intracerebroventricular (ICV) administration of peptide or prostaglandins which reduce experimental ulceration, do so by enhancing certain aspects of mucosal defense, inhibition of acid secretion, stimulation of bicarbonate and mocus of secretion and maintenance of morosal blood flow. These effects may be mediated by change in gastic monosal prosteplandin activity; 2) that ICV administration of peptides which potentiate experimental ulceration do so by reducing mocosal defense, stimlation of gastric acid secretion, inhibition of gastric bicrbonate and mucus production and reduction in morosal blood flow. Protective compounds given ICV include neurotensin, bombesin, opioids, calcitonin, calcitonin gene related peptide, and prostaglandins E2, T2, and F2. Compounds which potentiate injury, given ICV, include thyrotropin relleasing hormone and vasoactive intestinal polypeptide. Compounds will be given ICV to rats prior to placing them in cold restraint stress or administration of 50% ethanol, acidified aspirin (20 mM) or acidified taurocholate (10mM) orally. The effect of each ICV administered compound will also be studied for its effect on mucosal blood flow measured by hydrogen gas clearance, bicarbonate secretion using a gasometer of pH-stat technique, mucus production measuring the thickness of gel mucus optically and soluble mucus as glucosamine output, and acid secretion by gravity drainage in chronic dogs prepared with a gastric fistula. In addition, the effect of these ICV administered compounds on gastric mucosal prostaglandin activity will be studied using the prostaglandin-generation technique and RIA. These observations should indicate in which instance ICV administered peptides modulate gastric mucosal defensive functions through an endogenous prostaglandin-mediated mechanism. Dose response relationships will be demonstrated. Verification of the central effect will require that peripheral administration of these compounds do not cause similar effects on gastric mucosal functions.

这些研究旨在评估中央的作用 胃粘膜防御功能中的神经系统， 尊重神经肽和前列腺素。 它是假设的 1）脑室内（ICV）肽或 减少实验性溃疡的前列腺素，通过 增强粘膜防御的某些方面，抑制酸 分泌，碳酸氢盐刺激和分泌的渗透 维持病变血流。 这些影响可能是 通过变化的gasto虫前列腺素活性介导； 2） ICV给药的肽 实验性溃疡是通过减少Mocosal防御的方法来做到的 胃酸分泌的刺激，抑制胃酸 双碳酸盐和粘液产生以及莫尔索尔血液的减少 流动。 给定ICV的保护性化合物包括神经素， 孟买，阿片类药物，降钙素，降钙素基因相关的肽和 前列腺素E2，T2和F2。 增强的化合物 受伤给定ICV，包括甲状腺蛋白的激素和激素和 血管活性肠多肽。 化合物将得到ICV 将大鼠放在冷约束压力或 给药50％乙醇，酸化的阿司匹林（20毫米）或 酸化的牛角酸盐（10mm）。 每个ICV的效果 还将研究管理化合物的影响 通过氢气清除测量的粘膜血流， 使用pH-stat技术气表的碳酸氢盐分泌， 粘液产生测量凝胶粘液的厚度 和可溶性粘液作为葡萄糖输出，以及酸分泌 用胃瘘制成的慢性狗的重力引流。 另外，这些ICV给予的化合物对 胃粘膜前列腺素活性将使用 前列腺素生成技术和RIA。 这些观察 应指示在哪种实例ICV施用的肽 通过一个调节胃粘膜防御功能 内源性前列腺素介导的机制。 剂量反应 关系将被证明。 中央验证 效果将需要对这些的外围给药 化合物不会对胃粘膜产生类似的影响 功能。