MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

我们最近的研究集中在颗粒背后的过程 激素的组装、合成和插入颗粒，运动 颗粒到分泌物的部位和信号导致膜接触和 颗粒与质膜的融合导致胞吐作用 郎格罕的嗜铬细胞和胰岛。我们今年的工作包括 蛋白激酶的特性及其在激素中的可能作用 嗜铬细胞的分泌物。在嗜铬细胞中，佛波酯， TPA可诱导A23187，但不能诱导卡巴胆碱和高K+诱导的儿茶酚胺 分泌物。一致地，TPA也增强了钙离子诱导儿茶酚胺 从洋地黄素渗透的细胞中释放。肌醇磷脂代谢， 被认为是蛋白激酶C系统固有的，已被发现 当分泌发生时发生，但以延迟的方式发生，这表明它也 参与细胞功能的其他方面。Synexin，被认为是 参与分泌细胞的膜融合，已被发现与 钙依赖性嗜铬细胞质膜的内部结构 方式，而且将嗜铬颗粒膜系统融合在 不依赖钙的方式。分泌嗜铬细胞也一直是 通过电子能量损失成像低原子序数元素 光谱学。抗坏血酸和糖皮质激素已被证明可以调节 肾上腺嗜铬细胞培养中儿茶酚胺的生物合成。在小岛上 对于朗格汉斯，人们已经发现邻近的细胞是电性的 结合在一起，降温解离葡萄糖诱导的胰岛素释放 跨胰岛质膜的电活动。葡萄糖被发现是 引起K+浓度的节律性变化，与破裂相一致 电活动的模式。葡萄糖诱导的电学模型 研究了胰岛细胞膜离子通透性的变化。这个 糖尿病小鼠突变体Ob/ob的膜缺陷已定位于 包括K+通道。

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.