MECHANISMS OF HORMONE AND TRANSMITTER SECRETION

激素和递质分泌机制

• 批准号: 5201921
• 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/5201921
• 关键词: alloxan; amyloid proteins; annexins; ascorbate; calcium flux; chloride channels; chromaffin cells; cytochrome b; exocytosis; genetic mapping; glucose metabolism; granule; hormone regulation /control mechanism; human genetic material tag; human subject; human tissue; insulin; laboratory mouse; laboratory rat; membrane potentials; membrane transport proteins; molecular cloning; pancreatic islets; potassium channel; secretion

The human and mouse synexin genes were sequenced, and assigned to homologous chromosomes. The human gene was located at position 10q21.1- 21.2, while the mouse gene was located on chromosome homologous 14. The synexin genes were found to be highly homologous in terms of splice junction location, but quite distinct from the organization of other members of the annexin family. The half life of synexin was found to be ca. 40 h, and inhibitors of protein synthesis blocked secretion from bovine chromaffin cells in an appreciably shorter time. Thus, in addition to synexin other proteins are required for the secretory process. Human cytochrome b 561, a major transmembrane protein of chromaffin granules, was found to have 5 transmembrane domains rather than the six previously hypothsized. membrane potential was found to regulate cytoplasmic calcium oscillations in pituitary gonadoptrophs. M3-muscarinic receptors were found to potentiate glucose-induced insulin release from rat islets. The diabetogenic agent alloxan was found to activate K (ATP) channels in mouse pancreatic beta cells. A novel, cerebrospinal/vascular shunt was developed to implant xenobiotic islets in diabetic animals. Human pancreatic islets were analyzed by electrophysiologic methods for the first time. Evidence was obtained that 1CRAC currents control electrical activity in islets through effects on cholinergic receptors. A geometric sequence (the three-halves rule) was developed which accurately describes allowed multiple conductance states of ion channels. A theoretical model of the ion channel structure of the amyloid beta protein was constructed. A xanthine drug (CPX) and an analog compound (DAX) were found to activate chloride efflux from cystic fibrosis cells. An IND was filed with the FDA and clinical testing is planned. Uptake of ascorbate and dehydroascorbate were found to be taken up by fibroblasts by separate mechanisms.

对人和小鼠共联蛋白基因进行测序，并将其分配给 同源染色体 人类基因位于10q21.1-位置 21.2，而小鼠基因位于同源染色体14上。 的 共联蛋白基因在剪接方面高度同源 交叉点位置，但与其他组织截然不同 膜联蛋白家族成员。 共联蛋白的半衰期被发现是 约40 h，蛋白质合成抑制剂阻断了 牛嗜铬细胞在明显较短的时间。 因此在 除了共联蛋白外， 过程 人细胞色素B 561，一种主要的跨膜蛋白， 嗜铬颗粒，发现有5个跨膜结构域， 比之前假设的六个要多。 发现膜电位 调节垂体促性腺激素细胞的细胞质钙振荡。 发现M3-毒蕈碱受体增强葡萄糖诱导的胰岛素 从大鼠胰岛中释放。 发现致糖尿病剂四氧嘧啶 激活小鼠胰腺β细胞中的K（ATP）通道。 一本小说， 开发了脑脊髓/血管分流术以植入异生物质胰岛 在糖尿病动物中。 人胰岛通过以下方法分析： 电生理学方法。 证据是 1CRAC电流通过影响胰岛的电活动， 对胆碱能受体的影响 三等分规则（Three-halves rule） 它准确地描述了允许的多电导 离子通道的状态。 离子通道结构的理论模型 淀粉样β蛋白的结构。 一种黄嘌呤药物（CPX）， 一种类似化合物（DAX）被发现激活氯流出， 囊性纤维化细胞 向FDA提交了IND， 测试计划。 发现抗坏血酸和脱氢抗坏血酸的摄取 通过不同的机制被成纤维细胞吸收。