CENTRAL NEURAL CONTROL OF GASTRIC MUCOSAL DEFENSE

胃粘膜防御的中枢神经控制

基本信息

批准号：
2770371
负责人：
GORDON L KAUFFMAN
金额：
$ 19.7万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-01-01 至 2000-08-31
项目状态：
已结题

项目摘要

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.

神经素（NT）施用到多巴胺（DA）中边系统的核；伏隔核（NACB）和腹侧支段区域（VTA）;在大脑中抑制胃酸的分泌和提供胃粘膜防止冷水约束（CWR）诱发胃粘膜损伤。统一的假设是诱导的体温过低可通过通过中溶液系统中的NT活性来降低NT活性减少NT消息，导致多巴胺活性减少和A 在这些核中降低α和β肾上腺素能活性以增加迷走语调或同情性语气的降低然后导致胃酸分泌率提高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的中左右水平的影响 mRNA和B-MAX和K-D用于NT和DA受体； 2）扮演的角色中央肾上腺素能和多巴胺能受体激活； 3） NT增强胃粘膜前列腺素活性的机制。中脑纤维NT，DA和NT mRNA和NT和DA受体的浓度数字（B-Max）和亲和力（K-d）将在不同时间进行测量 CWR期间的间隔（15-120分钟）和立体定位之后将NT，DA或特定受体拮抗剂施用到NACB 或VTA。这些研究将提供有关NT在 CWR和NT和DA受体的控制过程中的中唇核 CWR期间的活动。中央（中唇）或全身预处理 alpha1，alpha2，beta1，beta2，da1或da2受体激动剂，拮抗剂，和1）中央NT给药之前的截短迷走神经切开术，然后进行CWR；或2）Pentagastrin管理将提供有关中央肾上腺素能和多巴胺能介导的作用中央新罕布什尔州的保护作用。特定药理的影响 NT中央之前管理，关于胃粘膜前列腺素的生成有关中央NT的潜在机制的信息增强胃粘膜前列腺素产生。这些研究会增强我们对胃粘膜功能中心控制的理解并可能提供粘膜防御机制可以通过的新途径得到增强。