MECHANISM OF CATECHOLAMINE SECRETION

儿茶酚胺的分泌机制

• 批准号: 3336737
• 负责人: ARUN R. WAKADE
• 金额: $ 16.2万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336737
• 关键词: adrenal medulla; adrenergic agents; adrenergic receptor; alpha antiadrenergic agent; anticholinergic agent; calcium channel; catecholamine inhibitor; catecholamines; cholinergic agents; chromaffin cells; cyclic AMP; cyclic GMP; denervation; enzyme inhibitors; exocytosis; forskolin; inositol phosphates; laboratory rat; membrane channels; muscarine; muscarinic receptor; neuronal transport; neuropeptides; neuropharmacology; nicotine; nicotinic receptors; norepinephrine; peripheral nervous system; protein kinase C; radiotracer; secretion; splanchnic nerves; sympathetic nervous system; synapses; tissue /cell culture

Chromaffin cells of the adrenal medulla continue to serve as a powerful tool to explore the field of neurohumoral secretion. In 1981 PI introduced a preparation to study catecholamine (CA) secretion from the isolated perfused adrenal gland of the rat. Using this preparation a number of physiological and pharmacological properties of secretion have been established. Most recently, several new observations have been made which made, which are of potential importance. The observations are as follows: 1) Secretion of CA is induced by nicotine as well as muscarine. Nicotine enhances influx of Ca45, whereas muscarine does not, although muscarine-evoked secretion is dependent on calcium. Nicotine-evoked secretion is desensitized within 20 min but muscarine-evoked is not up to 45 min. - a possibility of differential routes of mobilization of calcium and its utilization in exocytosis. 2) As long as 2 hr of continuous perfusion with 55 mM K-Krebs solution causes a pronounced secretion of CA, with only a modest degree of desensitization. Excess K-evoked secretion is totally dependent on calcium - a possibility of slow inactivation of calcium channels. 3) A marked secretion of CA obtained during perfusion with 55 mM K-Krebs solution is not associated with a reduction in the medullary CA content; however, after blockade of tyrosine hydroxylase there was a significant reduction in CA content - a possibility of reutilization of chromaffin storage vesicles. 4) Secretion of CA evoked by stimulation of splanchnic nerves at higher frequencies is more effectively reduced by cholinergic receptor antagonists than that evoked at lower frequencies - a possibility of another transmitter, in addition to acetylcholine, (ACh), released from splanchnic nerves to evoke secretion of CA. 5) Protein kinase C activator (phorbol esters) potentiate CA secretion and Ca45 uptake initiated by nicotine. Phorbol esters have no effect on muscarine-evoked secretion. cAMP activator (forskolin) potentiates CA secretion evoked by nicotine as well as muscarine - a possibility of intracellular messengers participating at different steps of exocytosis to evoke secretion. Biochemical, physiological and pharmacological experiments have been designed to discern each of the above possibilities in hope of extending our understanding of the secretory mechanism.

肾上腺髓质的嗜铬细胞继续充当 探索神经体液分泌领域的有力工具。 在 1981 PI推出研究儿茶酚胺（CA）的制剂 大鼠分离的灌注肾上腺的分泌物。 使用该制剂可产生多种生理和 分泌物的药理学特性已经确定。 最近，出现了一些新的观察结果 制作的，具有潜在的重要性。 观察结果如下 如下： 1) CA 的分泌是由尼古丁和尼古丁诱导的 毒蕈碱。 尼古丁增强 Ca45 的流入，而毒蕈碱 不会，尽管毒蕈碱诱发的分泌取决于 钙。 尼古丁诱发的分泌在 20 分钟内脱敏 但毒蕈碱诱发时间不超过 45 分钟。 - 有可能 钙的动员及其利用的不同途径 胞吐作用。 2) 只要​​连续灌注 55 mM 2 小时 K-Krebs 溶液引起 CA 的显着分泌，仅 适度的脱敏。 过量 K 诱发的分泌是 完全依赖于钙 - 缓慢失活的可能性 钙通道。 3) 期间获得的CA显着分泌 用 55 mM K-Krebs 溶液灌注与 降低髓质CA含量；然而封锁之后 酪氨酸羟化酶的 CA 显着减少 内容 - 铬蜡存储再利用的可能性 囊泡。 4) 刺激内脏引起CA的分泌 较高频率的神经可以更有效地减少 胆碱能受体拮抗剂比在较低条件下引起的胆碱能受体拮抗剂 频率 - 除了频率之外，还可以使用另一个发射器 乙酰胆碱（ACh），从内脏神经释放以唤起 CA 的分泌。 5) 蛋白激酶C激活剂（佛波酯） 增强尼古丁引发的 CA 分泌和 Ca45 吸收。 佛波酯对毒蕈碱诱发的分泌没有影响。 cAMP 激活剂（毛喉素）增强 CA 分泌 尼古丁和毒蕈碱 - 细胞内的可能性 参与胞吐作用不同步骤的信使 分泌。 生物化学、生理学和药理学 实验旨在辨别上述每一项 的可能性，希望扩大我们的理解 分泌机制。