MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

激素和递质分泌机制

• 批准号: 3917564
• 负责人: H B POLLARD
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3917564
• 关键词: adrenal glands; binding proteins; calcium binding protein; calcium channel; cell membrane; chromaffin cells; electron microscopy; exocytosis; freeze etching; granule; hormone biosynthesis; hormones; laboratory rat; membrane activity; membrane fusion; membrane permeability; membrane proteins; neuromuscular junction; orphan disease /drug; pancreatic islets; pinocytosis; potassium channel; secretion; tissue /cell culture; trachea; voltage /patch clamp

Our recent work has focussed on the processes leading to fusion between granule and plasma membranes during exocytosis in cells such as chromaffin cells, beta cells in islets of Langerhans, frog neuromuscular junction, and tracheal submucosal gland cells. Synexin, a calcium binding membrane fusion protein found in many tissues, was found to fuse membranes by a mechanism involving membrane mixing occurring prior to volume mixing. Synexin was also found to enter membranes and change the capacitance, and simultaneously to exhibit calcium channel activity. From these and other data we have formulated a hydrophobic bridge hypothesis for membrane fusion driven by synexin. The fast-freeze electron microscopy technique has been used to measure changes in distribution of elements and their concentrations in discrete regions of cytosol alkalinization of chromaffin granules suppresses secretion, implicating the state of the granule interior in the exocytosis process. Metalloendoprotease inhibitors block secretions by accelerating calcium efflux. Calcium enters chromaffin cells through a variety of voltage sensitive calcium channels, including at least one that is insensitive to dihydro- pyridines or w-conotoxin. In islet of Langerhans, fetal B-cells have functional ATP blockable channels, but still respond poorly to glucose. Cyclic Amp may potentiate insulin secretion by enhancing coupling between cells. Potassium channels from internal organelles of nerve endings can be reconstituted using a patch pipet technique.

我们最近的工作集中在导致核聚变的过程上 在细胞胞吐过程中颗粒和质膜之间的相互作用 例如嗜铬细胞、胰岛中的β细胞、青蛙 神经肌肉接头和气管粘膜下腺细胞。 Synexin是一种钙结合膜融合蛋白，存在于许多细胞中 组织，被发现通过一种机制融合膜， 在体积混合之前发生膜混合。 Synexin也是 发现进入膜并改变电容， 同时表现出钙通道活性。 从这些 和其他数据，我们制定了一个疏水桥假说， 由共联蛋白驱动的膜融合。 快速冻结电子 显微镜技术已被用于测量的变化， 元素的分布及其浓度在离散 嗜铬颗粒细胞质碱化区 抑制分泌，暗示颗粒内部的状态 在胞吐过程中。 金属内切蛋白酶抑制剂阻断 通过加速钙外流来分泌。 钙进入 嗜铬细胞通过各种电压敏感的钙 通道，包括至少一个对二氢- 吡啶类或ω-芋螺毒素。 在朗格汉斯岛中，胎儿B细胞 有功能性ATP可阻断通道，但反应仍然很差 葡萄糖。 环丙沙星可能通过以下途径增强胰岛素分泌： 增强细胞之间的耦合。 钾离子通道 神经末梢的细胞器可以用一个贴片 移液技术