MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

激素和递质分泌机制

• 批准号: 4689402
• 负责人: H B POLLARD
• 金额: --
• 依托单位: NAT INST OF ARTHRITIS, DIABETES, DIGESTIVE & 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/4689402
• 关键词: adrenal glands; ascorbate; calcium metabolism; catecholamines; cell biology; cell membrane; chromaffin cells; cytogenetics; electron microscopy; exocytosis; freeze etching; granule; hormone biosynthesis; hormones; insulin; membrane activity; membrane fusion; membrane permeability; monoclonal antibody; norepinephrine; orphan disease /drug; pancreatic islet function; pancreatic islets; pinocytosis; secretion; tissue /cell culture

Our recent studies have focused on the processes underlying granule assembly, synthesis and insertion of hormones into granules, movement of granules to sites of secretion and signals leading to membrane contact and fusion between granules and plasma membranes leading to exocytosis in chromaffin cells and Islets of Langerhans. Our work this year has included the characterization of protein kinase and its possible role in hormone secretion from chromaffin cells. In chromaffin cells, the phorbol ester, TPA, induces A23187 but not carbachol and high K+ induced catecholamine secretion. Consistently, TPA also enhanced Ca++ induced catecholamine release from digitonin-permeabilized cells. Phosphoinositide metabolism, believed to be intrinsic to protein kinase C systems, has been found to occur when secretion occurs, but in a delayed fashion, suggesting it also be involved with other aspects of cell function. Synexin, thought to be involved with membrane fusion in secreting cells, has been found to bind to the inner aspect of chromaffin cell plasma membrane in a calcium dependent manner, but also to fuse a chromaffin granule membrane system in a calcium-independent manner. Secreting chromaffin cells have also been mapped by imaging low atomic number elements by electron energy loss spectroscopy. Ascorbate and glucocorticoids have been shown to regulate catecholamine biosynthesis in cultured adrenal chromaffin cells. In islets of Langerhans, it has been found that neighboring cells are electrically coupled, and that cooling dissociates glucose induced insulin release from electrical activity across islet plasma membranes. Glucose was found to cause a rhythmic changes in K+ concentration, coincident with busting pattern of electrical activity. An electrical model for glucose-induced changes in membrane ionic permeability in islets has been devised. The membrane defect in the diabetic mouse mutant Ob/ob has been localized to include K+ channels.

我们最近的研究主要集中在颗粒的过程 组装，合成和插入激素进入颗粒，运动的 颗粒的分泌和信号的网站，导致膜接触， 颗粒和质膜之间的融合导致胞吐作用， 嗜铬细胞和胰岛。 我们今年的工作包括 蛋白激酶特性及其在激素中的可能作用 嗜铬细胞分泌物。 在嗜铬细胞中，佛波酯， TPA诱导A23187，但不诱导卡巴胆碱和高K+诱导的儿茶酚胺 分泌物 TPA对Ca~（2+）诱导的儿茶酚胺升高也有增强作用 从毛地黄皂苷透化的细胞中释放。 磷酸肌醇代谢， 被认为是蛋白激酶C系统固有的，已经发现 当分泌发生时发生，但以延迟的方式，这表明它也 参与细胞功能的其他方面。 Synexin被认为是 在分泌细胞中与膜融合有关，已被发现与 嗜铬细胞质膜内面呈钙依赖性 方式，而且还融合嗜铬颗粒膜系统， 不依赖钙的方式。 分泌嗜铬细胞也被 通过电子能量损失对低原子序数元素成像而绘制的 谱 抗坏血酸和糖皮质激素已被证明可以调节 培养的肾上腺嗜铬细胞中的儿茶酚胺生物合成。 胰岛中 根据Langerhans，已经发现相邻的细胞是电连接的。 耦合，并且冷却使葡萄糖诱导的胰岛素释放从 跨胰岛细胞膜的电活动。 发现葡萄糖 引起K+浓度的节律性变化，与破裂相一致 电活动模式。 葡萄糖诱导的电模型 已经设计了胰岛中膜离子渗透性的变化。 的 糖尿病小鼠突变体Ob/ob中的膜缺陷已被定位为 包括K+通道。