CENTRAL NEURAL CONTROL OF GASTRIC MUCOSAL DEFENSE

神经降压素(NT)对多巴胺(DA)的作用 中脑边缘系统的核；伏隔核(NACB)和腹侧 大脑中的被盖区(VTA)；抑制胃酸分泌和 对冷水束缚(CWR)的胃粘膜提供保护 致胃粘膜损伤。统一的假设是CWR- 诱导低温通过以下途径降低中脑边缘系统NT活性 减少NT消息，导致多巴胺活性降低和 这些核团中α和β肾上腺素能活动的降低导致 无论是迷走神经张力增加还是交感神经张力降低都会 从而导致胃酸分泌率增加或减少 内源性粘膜前列腺素合成。拟议的研究将 更好地定义L)CWR对中脑边缘NT、DA和NT水平的影响 NT和DA受体的mRNA及B-max和K-D；2) 中枢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(S)。 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期间和立体定位术后的间隔(15-120分钟) NACB内注射NT、DA或特异性受体拮抗剂 或者VTA。这些研究将提供关于NT在 中脑边缘核团与NT、DA受体的调控 无缝线路运行期间的活动。中枢性(中边缘)或全身性预处理 α1、α2、β1、β2、DA1或DA2受体激动剂、拮抗剂， 1)中央给药前切断迷走神经干，然后行CWR； 或2)五肽胃泌素给药将提供有关 中枢肾上腺素能和多巴胺能介导的抗分泌和抗衰老作用 中枢神经营养素的保护作用。特定药理作用的研究 中枢性迷走神经切断前的多巴胺能、肾上腺素能和主干迷走神经切断 给药后，对胃粘膜前列腺素的生成将提供 关于中央NT的潜在机制的信息(S) 促进胃粘膜前列腺素的生成。这些研究将 加深对胃粘膜功能中枢调控的认识 并可能提供新的途径，通过这些途径，粘膜防御机制可以 得到加强。

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.