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.

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