MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

激素和递质分泌机制

• 批准号: 3940462
• 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/3940462
• 关键词: adrenal glands; ascorbate; catecholamines; cell membrane; chromaffin cells; cytogenetics; electron microscopy; exocytosis; freeze etching; granule; hormone biosynthesis; hormones; insulin; membrane activity; membrane fusion; membrane permeability; membrane potentials; monoclonal antibody; nicotine; norepinephrine; orphan disease /drug; pancreatic islet function; pancreatic islets; pinocytosis; secretion; tissue /cell culture

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 distribution of elements and their concentrations in discrete regions of cytosol. By this method we have measured transmembrane electrical potentials across organelles in cells frozen with in a millisecond. Bovine chromaffin cells have been transplanted into regions of brain involved in pain. Stimulation of these implanted cells by nicotine administration causes a reduction in pain sensed by the recipient rats and monkeys. Cytosolic pH may be important in stimulus-secretion coupling in chromaffin and beta cells, resulting in release of adrenaline and insulin, respectively. Transient acidification is followed by promote return to ambient pH suing a Na+/H+-exchange pump in the plasma membrane. Ascorbate, an important vitamin, is critically required for biosynthesis of noradrenaline in chromaffin granules within intact chromaffin cells.

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， 许多组织，被发现通过一种机制融合膜 包括在体积混合之前发生的膜混合。 Synexin也被发现进入细胞膜并改变细胞的结构。 电容，同时表现出钙通道 活动 从这些和其他数据，我们制定了一个 膜融合疏水桥假说 共联蛋白 快速冷冻电子显微镜技术已被 用于测量元素分布及其浓度 在胞质溶胶的离散区域中。 通过这种方法，我们测量了 跨细胞器的跨膜电位 瞬间冻结 牛的嗜铬细胞 移植到大脑中与疼痛有关的区域 刺激 这些植入的细胞通过尼古丁给药引起 减少受体大鼠和猴子的疼痛感。 胞浆pH值可能是重要的刺激分泌偶联， 嗜铬细胞和β细胞，导致肾上腺素的释放， 胰岛素，分别。 瞬时酸化之后， 使用Na+/H+交换泵促进pH值恢复到环境pH值， 质膜。 抗坏血酸是一种重要的维生素， 是嗜铬细胞中去甲肾上腺素生物合成的关键 完整的嗜铬细胞内的颗粒。