CHOLECYSTOKININ--ROLE IN POSTPRANDIAL GASTRIC MOTILITY

胆囊收缩素——在餐后胃动力中的作用

• 批准号: 2141570
• 负责人: Helen E Raybould
• 金额: $ 16.14万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2141570
• 关键词: afferent nerve; biological models; biological signal transduction; brain stem; cholecystokinin; denervation; dietary carbohydrates; dietary lipid; electrophysiology; gastrointestinal epithelium; gastrointestinal motility /pressure; gastrointestinal nutrient absorption; glucose transporter; hormone receptor; hormone regulation /control mechanism; laboratory rat; membrane transport proteins; mucosa; neurons; nutrition related tag; receptor expression; sensory feedback; sodium; spinal reflex; vagus nerve; afferent nerve; biological models; biological signal transduction; brain stem; cholecystokinin; denervation; dietary carbohydrates; dietary lipid; electrophysiology; gastrointestinal epithelium; gastrointestinal motility /pressure; gastrointestinal nutrient absorption; glucose transporter; hormone receptor; hormone regulation /control mechanism; laboratory rat; membrane transport proteins; mucosa; neurons; nutrition related tag; receptor expression; sensory feedback; sodium; spinal reflex; vagus nerve

The ability of nutrients in the intestinal lumen to exert negative feedback control over proximal gastrointestinal function is well recognized, yet the control mechanisms are poorly defined. Extrinsic sensory pathways from the intestine and CCK are required for this regulatory process. The interaction between CCK and activation of intestinal sensory neurons is the focus of this proposal, which addresses the fundamental mechanism by which lumenal events are signalled to extrinsic sensory nerves. The hypothesis to be tested is that nutrients in the intestinal lumen stimulate from endocrine cells release of CCK that acts locally to stimulate intestinal sensory terminals resulting in reflex changes in gastric function. To test this hypothesis, studies with the following specific aims are proposed: (1) to determine that increased discharge in afferents in response to intestinal nutrients is dependent on CCK A receptor activation; (2) to determine that the functional response (inhibition of gastric motor function) to intestinal nutrients is dependent on a post-absorptive signal; and (3) to determine that activation of sensory pathways by intestinal nutrients alters gastric function via vagal and spinal reflex pathways. A combined experimental approach using electrophysiological recording of vagal afferent fiber discharge, in vivo physiology and functional anatomy of reflex pathways using Fos protein immunoreactivity as a marker for cell activation will be used to address these specific aims. The proposal is focused on determining a fundamental mechanism by which changes in lumenal content are signalled to afferent terminals located in the mucosal epithelium. This process is important in the regulation of normal digestive function. In addition, these mechanism may be disturbed in clinical condiitons were feedback from the intestine may be altered such as following abdominal surgery, alterations in feeding behaviors, such as obesity, anorexia and bulimia, and in functional bowel disease.

肠腔中营养物质发挥负的能力 对近端胃肠道功能的反馈控制很好 公认的，但是控制机制的定义很差。 外在 为此，需要从肠子和CCK的感觉途径 监管过程。 CCK与激活之间的相互作用 肠道感官神经元是该提案的重点，该提议解决了 发出信号事件的基本机制 外部感觉神经。 要检验的假设是 肠腔从内分泌细胞释放CCK的肠腔刺激 在本地作用以刺激肠道感觉终端，导致反射 胃功能的变化。 为了检验这一假设，研究了 提出了以下特定目标：（1）确定增加 响应肠道营养素的传入剂的排放取决于 CCK A受体激活； （2）确定功能响应 （抑制胃运动功能）对肠道营养素取决于 在吸收后信号上； （3）确定激活 肠道营养物质的感觉途径通过迷走神经胃功能改变 和脊柱反射途径。 使用的合并实验方法 迷走神经传入纤维排放的电生理记录，体内 使用FOS蛋白的反射途径的生理和功能解剖结构 免疫反应性作为细胞激活的标记物将用于解决 这些具体目标。 该提案的重点是确定基本 腔内含量变化的机制发出信号为传入 末端位于粘膜上皮。 这个过程很重要 正常消化功能的调节。 另外，这些机制 可能会在临床孔室中受到干扰 可能会改变，例如进行腹部手术，进食改变 行为，例如肥胖，厌食和贪食症，以及在功能性肠中 疾病。