CENTRAL NEURAL CONTROL OF GASTRIC MUCOSAL DEFENSE

胃粘膜防御的中枢神经控制

• 批准号: 3237457
• 负责人: GORDON L KAUFFMAN
• 金额: $ 20.03万
• 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 1989-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3237457
• 关键词: acidity /alkalinity; aminoacid analyzer; antiulcer drug; aspirin; bicarbonates; blood flow measurement; calcitonin; calcitonin gene related peptide; central nervous system; centrally acting drug; cerebrospinal fluid; drug administration routes; drug adverse effect; drug metabolism; ethanol; gastric acid; gastric mucosa; gastrointestinal circulation; gastrointestinal pharmacology; mucus; neural information processing; 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.

这些研究的目的是评估中央的作用， 神经系统在胃粘膜防御功能， 关于神经肽和胰头素。 据推测 1）脑室内（ICV）给药肽或 前列腺素可以通过以下方式减少实验性溃疡 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障碍， 维持血液流动。 这些影响可能是 由胃单核细胞前列腺素活性的变化介导; 2） ICV给药肽， 实验性溃疡通过减少粘膜防御来实现， 刺激胃酸分泌，抑制胃 碳酸氢盐和粘液的产生和减少 流 给予ICV的保护性化合物包括神经降压素， 蛙皮素，阿片类，降钙素，降钙素基因相关肽，和 E2、T2和F2。 增强 损伤，给予ICV，包括促甲状腺激素释放激素， 血管活性肠多肽 化合物将给予ICV 在将大鼠置于冷束缚应激之前， 给予50%乙醇、酸化阿司匹林（20 mM）或 酸化牛磺胆酸盐（10 mM）口服。 每个ICV的效果 还将研究施用的化合物对以下的影响： 通过氢气清除率测量粘膜血流量， 碳酸氢盐分泌使用pH-stat技术的气体计， 粘液产生光学测量凝胶粘液的厚度 和可溶性粘液作为葡萄糖胺输出， 重力引流在慢性狗准备与胃瘘。 此外，这些ICV给药的化合物对小鼠的作用也是显著的。 胃粘膜前列腺素活性将使用 三尖杉定生成技术和放射免疫分析。 这些观察结果 应指出在何种情况下ICV给予肽 调节胃粘膜防御功能， 内源性洋地黄素介导的机制。 剂量反应 关系将得到证明。 核查中央 效果将需要这些药物外周给药 化合物对胃粘膜不产生类似的作用 功能协调发展的