MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

我们的工作继续集中在导致融合的过程中 细胞胞吐分泌过程中的颗粒和质膜 包括嗜铬细胞、郎格汉斯胰岛的β细胞、神经 终末和囊性病变组织中的粘蛋白分泌细胞 纤维化症。分泌过程中的接触和融合过程可能是 由钙结合蛋白突触蛋白(Annexin VII)介导。我们有 了解到Annexin VII免疫定位于 嗜铬细胞的细胞质，包括嗜铬颗粒 膜。Annexins、I、II和V也可在这些和 其他细胞，但它们的分布与突触蛋白不同。 钾通道也被证明存在于嗜铬细胞颗粒上 膜，尽管它们对钙不敏感。的作用 这些途径可能是在回收颗粒中重新排列[K] 胞吐。在垂体促性腺激素中，钾通道控制着 膜电位对氨基精氨酸敏感，并调节振荡 膜电位和细胞内钙离子浓度。这一机制 这些细胞内钙的振荡依赖于IP3 新陈代谢。在朗格汉斯人的胰岛中，葡萄糖对 细胞内钙和分泌物。葡萄糖的稳态效应 就是诱导细胞内钙离子的节律性振荡 但葡萄糖最早的作用是降低 钙离子浓度。酵母己糖激酶转基因小鼠的研究 新生儿胰岛缺乏的胰岛素分泌，但 由催乳素的胰岛暴露引起的。我们还开发了 根据我们的观察，一种治疗囊性纤维化的潜在药物 A1受体拮抗剂8-环戊基-1，3-二丙基黄嘌呤激活 人上皮细胞和小鼠成纤维细胞系的氯离子外流 携带CFTR(Delta F508)突变，但不携带野生型CFTR。我们 还了解到阿尔茨海默氏症淀粉样蛋白形成离子 双分子膜中的通道，这一活性可能是 淀粉样蛋白在这种疾病中的神经毒性。

Our work continues to focus on the processes leading to fusion between granule and plasma membranes during exocytotic secretion from cells, including chromaffin cells, beta cells from Islets of Langerhans, nerve terminals, and mucin secreting cells from tissues affected by cystic fibrosis. The contact and fusion processes during secretion may be mediated by the calcium binding protein synexin (annexin VII). We have learned that Annexin VII is immunolocalized to formed elements in the cytoplasm of chromaffin cells, including the chromaffin granule membranes. Annexins, I, II and V can also be detected in these and other cells, but their distribution if different from that of synexin. Potassium channels have also been shown to occur on chromaffin granule membranes, although they are not sensitive to calcium. The role of these channels may be to rearrange [K] in recycling granules following exocytosis. In pituitary gonadotophs the potassium channels controlling the membrane potential are apamine sensitive, and regulate oscillations in membrane potential and internal calcium concentration. The mechanism of oscillation of calcium within these cells depends upon IP3 metabolism. In islets of Langerhans, glucose has a complex effect on intracellular calcium and secretion. The steady state effect of glucose is to induce rhythmic oscillations in intracellular calcium and electrical potential, but the earliest action of glucose is to lower the calcium ion concentration. A transgenic mouse with yeast hexokinase in the insulin secretion, which is lacking in neonatal islets, but is induced by exposure of the islets of prolactin. We have also developed a potential drug for cystic fibrosis based on our observation that the A1-receptor antagonist, 8-cyclopentyl-1,3-dipropyl xanthine activates chloride efflux from human epithelial and mouse fibroblast cell lines bearing the CFTR (delta F508) mutation but not the wild type CFTR. We have also learned that the Alzheimer's disease amyloid forms ion channels in bilayer membranes, and that this activity may be the basis of amyloid neurotoxicity in this disease.