PANCREATIC SECRETION--5HT SENSORY TRANSDUCTION MECHANISM

对餐后胰酶分泌的调节作用一直是 主要归因于荷尔蒙CCK和一种 激活胆碱能节后神经元的迷走神经-迷走神经反射 在胰腺里。最近，我们使用RT模型证明了 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 路径。CCK-8受体拮抗剂L364,718抑制75%和 高渗NaCI刺激80%的胰腺分泌 溶液和麦芽糖。大量5-羟色胺 在十二指肠近端可见含细胞。 肠子。我们推测5-羟色胺可能会从EC释放出来 肠道内的细胞，起传感器的作用，检测体内的临界物。 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引起胰腺酶 通过迷走神经传入途径分泌。我们将证明这一点 在麻醉和清醒的大鼠中，阈值刺激刺激 通过辣椒素敏感的传入迷走神经分泌胰酶 路径。我们计划将感受区定位到十二指肠 粘膜。5-羟色胺受体阻滞剂和5-羟色胺的应用研究 神经毒素将阐明粘膜释放的5-羟色胺在脑出血中的作用 调解这些反应。提供直接的神经生理学 有证据表明管腔刺激迷走神经传入通路， 鲁米那对迷走神经感觉神经元的单位放电反应 将记录非CCK依赖的刺激。5-羟色胺在血管紧张素转换酶中的作用 将对调解这些反应进行调查。的子类 对5-羟色胺敏感的迷走神经传入纤维将被识别 并检测其对CCK的敏感性。最后，我们将描述 CCK与非CCK依赖的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和 将提高对非CCK依赖的鲁米诺如何 刺激能刺激胰酶分泌素。

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.