CENTRAL NEURAL CONTROL OF GASTRIC MUCOSAL DEFENSE

这些研究旨在评估中央银行的作用 神经系统在胃粘膜防御功能中的作用 尊重神经肽和前列腺素。这是假设的 1)脑室(Icv)注射多肽或 前列腺素可以减少实验性溃疡，其作用是通过 增强某些方面的粘膜防御，抑制酸 分泌物、小苏打的刺激和分泌物的增多 维持躯体血流量。这些影响可能是 由胃单糖蛋白原活性变化所介导；2) 脑室注射的多肽可以增强 实验性溃疡通过减少局部防御来做到这一点， 抑制胃酸分泌，抑制胃酸分泌 血中小苏打和粘液的产生和减少 流。脑室注射的保护性化合物包括神经降压素， 蛙皮素、阿片类药物、降钙素、降钙素基因相关肽和 前列腺素E2、T2和F2。增强能力的化合物 脑室注射的损伤包括促甲状腺激素释放激素和 血管活性肠多肽。化合物将被给予icv 在将大鼠置于冷束缚应激或 注射50%乙醇、酸化阿司匹林(20 Mm)或 口服酸化牛磺胆酸盐(10 MM)。每个ICV的效果 给药的化合物也将被研究其对 用氢气清除法测量粘膜血流量， 使用pH-STAT技术的气体计分泌碳酸氢盐， 粘液产量用光学方法测量凝胶粘液厚度 和可溶性粘液作为氨基葡萄糖的输出，以及由 慢性胃瘘犬的重力引流。 此外，这些脑室给药化合物对 胃粘膜前列腺素活性将用 前列腺素生成技术和放射免疫分析。这些观察结果 应指明ICV在哪种情况下给药多肽 胃粘膜防御功能的调节 内源性前列腺素介导的机制。剂量反应 我们将展示他们的关系。对中央的核查 效果将需要这些药物外围给药 化合物不会对胃粘膜产生类似的影响 功能。

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.