NEUROENDOCRINE CONTROL OF SMALL INTESTINAL MOTILITY

小肠运动的神经内分泌控制

• 批准号: 3462846
• 负责人: THOMAS V NOWAK
• 金额: $ 9.37万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-20 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3462846
• 关键词: cholecystokinin; diabetes mellitus; electric field; electrostimulus; gastrointestinal motility /pressure; gastrointestinal pharmacology; hormone inhibitor; hormone regulation /control mechanism; ileum; laboratory rabbit; neural information processing; neuroendocrine system; neuromuscular transmission; neuropeptides; small intestines; substance P; vasoactive intestinal peptide

Both the intrinsic nerves and gut neuropeptides are known to regulate muscle contraction and relaxation in the small intestine. However, how nerves and peptides act together to regulate neuromuscular transmission is not well understood. The aim of this proposal is to define the neural and endocrine controls which regulate neuromuscular transmission in the rodent small intestine. Segments of duodenum and ileum are mounted in baths of Krebs solution gassed with 95% 0/2 - 5% Co/2 at 37/0 and stretched to optimal lengths. Each segment undergoes electrical field stimulation and the fluid bathing each segment is removed and assayed for vasoactive intestinal polypeptide (VIP), motilin, cholecystokinin, (CCK) and substance P. Atropine is used to study the effect of muscarinic blockade on neuropeptide release. Current amplitude during field stimulation is varied to selectively activate cholinergic excitatory nerves, non-cholinergic excitatory nerves, and non-cholinergic inhibitory nerves. A separate study examines the influence of neuropeptides and peptide antagonists or antisera on neuromuscular transmission. Circular and longitudinal muscle strips are stretched to optimal lengths and tensions are measured continuously. Resting and field-stimulated tensions are monitored as tissues are superfused with: 1) VIP, CCK, substance P, motilin, or met- and leu- enkephalin; 2) antisera to VIP, CCK, motilin, and substance P; 3) naloxone or proglumide. Current amplitude during field stimulation is varied to determine the effects of these agents on cholinergic excitatory nerves, non-cholinergic excitatory nerves, and non-cholinergic inhibitory nerves. Since preliminary observations suggest that current direction can preferentially activate excitatory or inhibitory nerves, a separate study examines the influence of directed electrical field stimulation applied at various current amplitudes on neuromuscular transmission. A final study examines enteric neuromuscular transmission in experimental diabetes mellitus. Neuropeptides release is studied in streptozotocin-treated rats, controls, and insulin-treated diabetic rats, while separate studies examine the effects of VIP, CCK, and motilin on enteric neuromuscular transmission in these animals. These experiments will help clarify the mechanism of neuropeptidergic transmission in the enteric nervous system. Ultimately, this study will help to better understand the pathophysiology of motor abnormalities such as intestinal pseudoobstruction, paralytic ileus, and diabetic enteropathy.

固有神经和肠道神经肽都知道 调节小肠的肌肉收缩和放松。 但是，神经和肽如何共同作用以调节 神经肌肉传播尚不清楚。 目的 该建议是定义神经和内分泌控制 调节啮齿动物小肠中的神经肌肉传播。 十二指肠和回肠的细分市场安装在克雷布斯的浴室中 溶液在37/0时以95％0/2-5％CO/2加热，并延伸至 最佳长度。 每个部分都经历电场 刺激和沐浴的流体被去除，然后 分析血管活性肠多肽（VIP），motilin， 胆囊菌素，（CCK）和物质P.阿托品用于研究 毒蕈碱阻断对神经肽释放的影响。 现场刺激期间的电流幅度变化为选择性 激活胆碱能兴奋性神经，非胆碱能兴奋性 神经和非胆碱能抑制神经。 另一项研究检查了神经肽和 神经肌肉传播的肽拮抗剂或抗血清。 循环和纵向肌肉条伸展至最佳 长度和张力是连续测量的。 休息和 当组织被超级融合时，监测场刺激的紧张局势 与：1）VIP，CCK，物质P，Motilin或Met-和Leu- Enkephalin; 2）抗血清到VIP，CCK，Motilin和p; 3） 纳洛酮或前珠。 现场振幅 刺激变化以确定这些药物对 胆碱能兴奋性神经，非胆碱能兴奋性神经， 和非胆碱能抑制神经。 自初步 观察表明，当前方向可以优先 激活兴奋性或抑制神经，这是一项单独的研究 检查定向电场刺激的影响 在神经肌肉上以各种电流振幅应用 传播。 最终研究检查了肠神经肌肉传播 实验性糖尿病。 研究神经肽释放 在链蛋白酶治疗的大鼠中，对照和胰岛素治疗 糖尿病大鼠，而单独的研究检查了VIP的影响，但 cck和在这些肠神经肌肉传播上的motilin 动物。 这些实验将有助于阐明 肠神经系统中的神经抑制剂传播。 最终，这项研究将有助于更好地了解 运动异常的病理生理，例如肠道 伪虫结构，麻痹性回肠和糖尿病肠病。