CENTRAL NEURAL CONTROL OF GASTRIC MUCOSAL DEFENSE

胃粘膜防御的中枢神经控制

• 批准号: 2518274
• 负责人: GORDON L KAUFFMAN
• 金额: $ 19.22万
• 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 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518274
• 关键词: 3,4 dihydroxyphenylacetate; dopamine agonists; dopamine antagonists; dopamine receptor; gastric acid; gastric mucosa; gastrins; gastrointestinal epithelium; hormone regulation /control mechanism; hypothermia; laboratory rat; messenger RNA; neuroregulation; neurotensin; norepinephrine; nucleus accumbens; polymerase chain reaction; prostaglandins; receptor expression; secretion; tegmentum; vagotomy; vagus nerve

Administration of neurotensin (NT) into the dopamine (DA)-containing nuclei of the mesolimbic system; nucleus accumbens (NACB) and ventral tegmental area (VTA); in the brain inhibits gastric acid secretion and affords gastric mucosal protection against cold water restraint (CWR) induced gastric mucosal injury. The unifying hypothesis is that CWR- induced hypothermia reduces NT activity in the mesolimbic system by reducing NT message, causing a reduction of dopamine activity and a reduction in alpha and beta adrenergic activity in these nuclei resulting in either increased vagal tone or decreased sympathetic tone which will then result in increased rates of gastric acid secretion or reduced endogenous mucosal prostaglandin synthesis. The proposed studies will better define l) the effect of CWR on mesolimbic levels of NT, DA, and NT mRNA and the B-max and K-D for NT and DA receptors; 2) the role played by central adrenergic and dopaminergic receptor activation; and 3) the mechanism(s) by which NT enhances gastric mucosal prostaglandin activity. Concentrations of mesolimbic NT, DA, and NT mRNA, and NT and DA receptor number (B-max) and affinity (K-D) will be measured at various time intervals (15-120 min) during CWR and following the stereotaxic administration of a NT, DA or specific receptor antagonists into the NACB or VTA. These studies will provide information regarding the role of NT in the mesolimbic nuclei during CWR and control of NT and DA receptor activity during CWR. Central (mesolimbic) or systemic pretreatment with alpha1, alpha2, beta1, beta2, DA1, or DA2 receptor agonists, antagonists, and truncal vagotomy before 1) central NT administration followed by CWR; or 2) pentagastrin administration will provide information regarding the role of central adrenergic and dopaminergic mediation of antisecretory and protective effects of central NT. The effect of specific pharmacological dopaminergic, adrenergic, and truncal vagotomy preceding central NT administration, on gastric mucosal prostaglandin generation will provide information regarding the potential mechanism(s) by which central NT enhances gastric mucosal prostaglandin generation. These studies will enhance our understanding of central control of gastric mucosal function and may provide new avenues through which mucosal defense mechanisms can be enhanced.

将神经降压素（NT）施用到含有多巴胺（DA）的 中脑边缘系统的核团;腹侧核（NACB）和 被盖区（VTA）;在大脑中抑制胃酸分泌， 提供胃粘膜保护免受冷水束缚（CWR） 引起胃粘膜损伤。统一的假设是，CWR- 诱导的低温降低了中脑边缘系统的NT活性， 减少NT信息，导致多巴胺活性降低， 这些核团中的α和β肾上腺素能活性降低， 迷走神经张力增加或交感神经张力降低， 然后导致胃酸分泌速率增加或减少 内源性粘膜前列腺素合成。拟议的研究将 更好地定义l）CWR对NT、DA和NT的中脑边缘水平的影响 2）神经递质在神经元中的作用; 中枢肾上腺素能和多巴胺能受体激活;和3） NT增强胃粘膜前列腺素活性的机制。 中脑边缘NT、DA和NT mRNA以及NT和DA受体的浓度 将在不同时间测量数量（B-max）和亲和力（K-D CWR期间和立体定位后的间隔（15-120 min） 将NT、DA或特异性受体拮抗剂施用到NACB中 或VTA。这些研究将提供有关NT在以下方面的作用的信息： CWR时中脑边缘核与NT和DA受体的调控 CWR期间的活动。中枢（中脑边缘）或全身预处理， α 1、α 2、β 1、β 2、DA 1或DA 2受体激动剂，拮抗剂， 迷走神经干切断术后1）给予中枢NT后进行CWR; 或2）五肽胃泌素管理将提供有关 中枢肾上腺素能和多巴胺能介导的抗分泌和 中央NT的保护作用。特定药理学作用 中枢NT前多巴胺、肾上腺素和迷走神经干切断术 给药，对胃粘膜前列腺素的产生将提供 关于中央NT的潜在机制的信息 增强胃粘膜前列腺素的生成。这些研究将 增强我们对胃粘膜功能中枢控制的理解 并可能提供新的途径，通过粘膜防御机制， 增强。