PANCREATIC SECRETION--5HT SENSORY TRANSDUCTION MECHANISM

胰腺分泌--5HT感觉传导机制

• 批准号: 6381305
• 负责人: YING LI
• 金额: $ 16万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6381305
• 关键词: autonomic reflex; biological signal transduction; body fluid osmolarity; chemical stimulation; cholecystokinin; digestion; exocrine glands; gastrointestinal hormones; gastrointestinal pharmacology; hormone receptor; laboratory rat; neuropeptide receptor; neurophysiology; neuroregulation; nutrient interaction; nutrition related tag; pancreas; secretin; secretion; sensory signal detection; serotonin; serotonin receptor; vagus nerve

Mediation of postprandial pancreatic enzyme secretion has been ascribed mainly to the hormone cholecystokinin (CCK) and to a vagal-vagal reflex that activate cholinergic post-ganglionic neurons in the pancreas. Recently using a rt model we have shown that does of CCK that produce physiological plasma CCK levels stimulate pancreatic enzyme secretion by acting on vagal afferent pathway. CCK-8 receptor antagonist L364,718 inhibited 75% and 80% of the pancreatic secretion stimulated by hyperosmolar NaCI solution and maltose respectively. Large amounts of 5-HT containing cells are found in the proximal duodenal area of the intestine. We hypothesize that 5-HT may be released from the EC cells lining the gut which act as a sensor to test liminal contents in response to luminal stimuli and that this interacts with the cabal afferent nerve endings in the mucosa to evoke pancreatic enzyme secretion via the vagal afferent pathway. We will demonstrate that in the anesthetized and conscious rats, liminal stimuli stimulate pancreatic enzyme secretion via a capsaicin-sensitive afferent vagal pathway. We plan to localize the receptive filed to the duodenal mucosa. Studies utilizing 5-HT receptor blockade and 5-HT neurotoxin will elucidate the role of mucosal released 5-HT in the mediation of these responses. To provide direct neuorphysiological evidence that luminal stimili stimulate vagal afferent pathway, unitary activities of sensory vagal neurons in response to luminal non-CCK dependent stimuli will be recorded. The role of 5-HT in mediating these responses will be investigated. The subclass of vagal afferent fibers which are sensitive to 5-HT will be identified and their sensitivity to CCK tested. Finally, we will delineate the interaction between CCK and non-CCK dependent luminal factors. These studies will have important physiological ramifications and will improve understanding of how non CCK-dependent luminal stimuli act to stimulate pancreatic enzyme secretin.

餐后胰腺酶分泌的调节已被 主要归因于激素胆囊收缩素（CCK）和 激活胆碱能节后神经元的迷走-迷走反射 在胰腺中。 最近，我们使用rt模型证明， 产生生理血浆CCK水平的CCK剂量 作用于迷走神经传入刺激胰酶分泌 通路 CCK-8受体拮抗剂L364，718抑制75%， 高渗NaCl刺激80%的胰腺分泌 溶液和麦芽糖。 大量的5-HT 含细胞被发现在近端十二指肠区的 肠子 我们推测，5-HT可能是从EC中释放出来的， 细胞内衬的肠道，作为传感器，以测试阈内容， 对管腔刺激的反应，这与阴谋集团相互作用， 粘膜中的传入神经末梢诱发胰酶 通过迷走神经传入途径分泌。 我们将证明， 在麻醉和清醒的大鼠中，阈刺激 辣椒素敏感性传入迷走神经分泌胰酶 通路 我们计划将感受野定位在十二指肠 粘膜 利用5-HT受体阻断剂和5-HT 神经毒素将阐明粘膜释放的5-HT在 调解这些反应。 提供直接的神经生理学 管腔刺激刺激迷走神经传入通路的证据， 迷走神经感觉神经元对管腔刺激反应的单一活动 将记录非CCK依赖性刺激。 5-羟色胺在 将调查这些反应的中介。 的子类 将鉴定对5-HT敏感的迷走神经传入纤维 并检测其对CCK的敏感性。 最后，我们将描绘 CCK和非CCK依赖性管腔因子之间的相互作用。 这些研究将产生重要的生理学影响， 将提高对非CCK依赖性管腔 刺激物起刺激胰酶分泌素作用。