Differential binding and release of norepinephrine and tachyphylaxis.
Differential binding and release of norepinephrine and tachyphylaxis.
复制标题
去甲肾上腺素的差异结合和释放以及快速耐受。
DOI：
10.1016/0006-2952(62)90082-5
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发表时间：
1962
影响因子：
5.8
通讯作者：
I. Kopin
中科院分区：
文献类型：
--
作者：
L. Potter;J. Axelrod;I. Kopin
拟交感胺类药物的快速耐受现象是多年来药理学研究的经典问题。伯恩和兰德提供了间接证据，表明某些拟交感神经胺通过从贮存中释放去甲肾上腺素来发挥作用。“最近，一些研究人员表明，快速耐受的发展后，拟交感胺的行动可以恢复去甲肾上腺素的管理。我们以前已经证明，~ 3-去甲肾上腺素从心脏的自发释放最初是快速的，然后逐渐变慢。p这表明H3-去甲肾上腺素被周转率快的商店吸收，然后逐渐进入周转率较慢的商店。Blaschko和Welch观察到，肾上腺髓质未变性颗粒中只有五分之一的升压胺在静脉注射后立即产生生理效应。[5]这篇文章将提供直接证据，表明去甲肾上腺素有两种储存方式，一种是容易释放的，另一种是紧密结合的。酪胺通过消耗更容易释放的去甲肾上腺素来产生快速耐受，本实验室以前的工作表明，酪胺从大鼠心脏释放H3-去甲肾上腺素。在给予10 mg/kg酪胺后，还发现大鼠心脏中内源性儿茶酚胺显著减少（图1）。在注射H3-去甲肾上腺素后15分钟开始，以1% min的间隔重复给予酪胺。在注射H_3-去甲肾上腺素后60分钟，测定心脏的H_3-去甲肾上腺素和内源性儿茶酚含量。
THE phenomenon of tachyphylaxis to sympathomimetic amines has been a classical problem in pharmacology for many years. Burn and Rand have provided indirect evidence showing that certain sympathomimetic amines exert their effects by the liberation of norepinephrine from stores.’Recently, several investigators have shown that after the development of tachyphylaxis the actions of sympathomimetic amines can be restored by the administration of norepinephrine. 2y a We have previously demonstrated that the spontaneous release of~ 3-norepinephrine from the heart is rapid at first and then becomes progressively slower. p This suggests that H3-norepinephrine is taken up by a store with rapid turnover rate and then gradually enters stores with slower turnover. Blaschko and Welch observed that only one-fifth of the pressor amines in the undenatured granule of the adrenal medulla had an immediate physiological effect after its intravenous administration. 5 This communication will provide direct evidence showing two kinds of stores of norepinephrine, one in which it is easily released and another in which it is tightly bound. Tyramine produces tachyphylaxis by depleting the more easily releasable store of norepinephrine.Previous work in this laboratory has shown that tyramine releases H3-norepinephrine from the rat heart.* A significant reduction of endogenous catecholamines in the rat heart was also found after the administration of 10 mg of tyramine per kg (Fig. 1). Tyramine was given repeatedly at 1% min intervals beginning 15 min after the injection of H3-norepinephrine. The hearts were assayed for HQorepinephrine’ and endogenous catecholaminess 60 min after the injection of H3-norepinephrine.