MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

激素和递质分泌机制

• 批准号: 3754075
• 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/3754075
• 关键词: Malacostraca; amyloid proteins; annexins; ascorbate; calcium; calcium metabolism; chromaffin cells; cytochrome b; cytogenetics; dopamine beta monooxygenase; drug receptors; exocytosis; genetic mapping; granule; hormone regulation /control mechanism; human genetic material tag; human subject; human tissue; laboratory mouse; laboratory rat; membrane channels; molecular cloning; pancreatic islets; secretion; vascular endothelium permeability

Regulation of secretory processes and the mechanisms of external activation and internal control by calcium continue to be the principal interests of the LCBG. In the classical chromaffin cell system we have found that the nicotinic receptor regulating secretion of chromaffin granule contents by exocytosis is itself controlled by sigma opiate receptors. Chromaffin granules contain dopamine monooxygenase (DBH) which is responsible for synthesis of noradrenaline. We found that external ATP regulates DBH function in chromaffin granules by a mechanism unrelated to effects of proton pumping. A major chromaffin granule membrane protein cytochrome b561 has been cloned and localized to human chromosome 17q11-qter. When the chromaffin cell is stimulated more granule contents are synthesized but cytochrome b561 levels maintained. The new vesicles apparently have greater secretory quanta. Islets of Langerhans secrete insulin in response to glucose and other stimuli. We found that both glucose- and muscarinic agonist-potentiated secretion is mediated by calcium from both intracellular and extracellular sources. Glucose sensing mechanisms in neonatal rat islets are non-functional, and are thought to model changes occurring during type II diabetes. However, glucose sensitivity can be prematurely induced by exposure of the islets to prolactin. Endothelial cells have been shown to form relatively impermeable sheets in culture, and to join together by lucifer yellow- delimited gap junctions. Albumin has a modulatory effect on endothelium permeability which is species specific. Ascorbic acid accumulation and recycling is enhanced in activated human neutrophils. In situ kinetics of ascorbate utilization can be used to evaluate true requirements for man. A toxic effect of ascorbate is the suppression of insulin secretion from isolated islets, and may be the basis for the tight control of blood levels in intact organisms. Calcium action during exocytotic control of blood levels in intact organisms. Calcium action during exocytotic membrane fusion may be controlled by synexin (annexin VII), and we have recently localized human synexin gene to chromosome 10q21.1-21.2. The structure of the gene varies from other members of the annexin gene family. In anticipation of studies with a synexin knockout mouse we have cloned synexin from mouse, and have characterized the mouse synexin genomic sequence. It is virtually identical to the human case. Calcium metabolism in muscle has also been studied with the local anesthetic tetracaine. Rynaodine receptors have also been characterized in lobster skeletal muscle. Finally, beta amyloid ion channels have been further characterized and evaluated as possible toxic agents in the genesis of Alzheimer's disease.

分泌过程的调控与外源激素的作用机制 钙激活和内控仍然是主要的 LCBG的利益。在经典的嗜铬细胞系统中，我们有 发现调节嗜铬细胞分泌的烟碱受体 通过胞吐作用产生的颗粒含量本身是由西格玛阿片控制的。 感受器。嗜铬粒含有多巴胺单加氧酶(DBH) 它负责合成去甲肾上腺素。我们发现 外源性三磷酸腺苷对嗜铬颗粒DBH功能的调节机制 与质子泵浦效应无关。一种主要的嗜铬颗粒 膜蛋白细胞色素b561已被克隆并定位于人 染色体17q11-QTER。当嗜铬细胞受到更多刺激时 合成颗粒内容物，但维持细胞色素b561水平。 新的囊泡显然有更大的分泌量。小岛： 朗格汉斯人对葡萄糖和其他刺激做出反应，会分泌胰岛素。我们 发现葡萄糖和毒扁豆碱激动剂增强的分泌物都是 由细胞内和细胞外来源的钙调节。 新生大鼠胰岛的葡萄糖感应机制是非功能性的，并且 被认为是II型糖尿病期间发生的变化的模型。然而， 胰岛暴露可过早地诱导葡萄糖敏感性 催乳素。内皮细胞已经被证明形成了相对 在培养中不透水的薄片，并由路西法黄色连接在一起- 分隔的缝隙连接。白蛋白对血管内皮细胞的调节作用 渗透性是物种特有的。抗坏血酸蓄积和 在激活的人类中性粒细胞中，循环利用得到了增强。原位动力学 抗坏血酸利用率可以用来评估 天哪。抗坏血酸的毒性作用是抑制胰岛素的分泌 来自孤立的胰岛，可能是严格控制血液的基础 在完整的生物体中的水平。钙在胞吐调控中的作用 完整生物体内的血液水平。钙在胞吐过程中的作用 膜融合可能由突触蛋白(Annexin VII)控制，我们有 最近将人类突触蛋白基因定位于染色体10q21.1-21.2。这个 该基因的结构与膜联蛋白基因的其他成员不同 一家人。在对Synexin基因敲除小鼠的研究中，我们有 克隆了小鼠突触蛋白，并对小鼠突触蛋白进行了鉴定 基因组序列。这与人类的情况几乎完全相同。钙 使用局部麻醉剂也研究了肌肉中的新陈代谢。 丁卡因。龙虾体内的Rynaodine受体也具有特征。 骨骼肌。最后，β-淀粉样蛋白离子通道进一步 表征和评估为可能的毒物在疾病的发生中 阿尔茨海默氏症。