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.

给药神经紧张素（NT）进入含多巴胺（DA）