NORADRENALINE - FATE AND CONTROL OF ITS BIOSYNTHESIS
NORADRENALINE - FATE AND CONTROL OF ITS BIOSYNTHESIS
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DOI：
10.1126/science.173.3997.598
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发表时间：
1971-01-01
期刊：
影响因子：
56.9
通讯作者：
AXELROD, J
中科院分区：
文献类型：
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作者：
AXELROD, J
在O-甲基化工作开始后不久，我们对肾上腺素在动物组织中的分布进行了研究。幸运的是，Seymour Kty安排合成了高比活性的去甲肾上腺素和肾上腺素，标记在7位。这使得给药生理量的神经递质和研究循环儿茶酚胺的定位和代谢成为可能。与Weil-Malherbe和Whitby合作，开发了测定组织中去甲肾上腺素和去甲肾上腺素及其0-甲基化代谢物的具体方法。猫静脉注射[3 H]肾上腺素(32)或[3 H]去甲肾上腺素(33)后，这些儿茶酚胺在组织中迅速而不均匀地分布。这些胺被选择性地摄取在交感神经(心脏、脾)高度支配的组织中。由于脑中存在可忽略不计的~3H标记儿茶酚胺类化合物，因此提示对这些化合物存在血脑屏障。组织中也存在甲基化的代谢物[~3H]去甲肾上腺素和[~3H]去甲肾上腺素。当给药儿茶酚胺2小时后检查组织时，在生理作用消失很久之后，发现它们的[~3H]肾上腺素和[~H]去甲肾上腺素水平与2分钟后几乎相同。这些实验表明去甲肾上腺素和肾上腺素是以非生理活性的形式被摄取和保留在组织中的。儿茶酚胺与高肾上腺素能神经组织的选择性结合指向交感神经为滞留部位。为了验证这种可能性，猫一侧切除颈上神经节，等待足够的时间(7天)使交感神经纤维完全变性。然后静脉注射去甲肾上腺素，1小时后处死动物，并注射[~3H]儿茶酚胺。
Soon after the work on O-methyla-tion was begun, the distribution of adrenaline in animal tissueswas investi-gated. Fortunately, Seymour Kety arranged for the synthesis of tritiated noradrenaline and adrenaline of high specific activity labeled at the 7-position. This made possible the administration of physiological amounts of the neurotransmitter and a study of the localization andmetabolism of the cir-culating catecholamine. In collaboration with Weil-Malherbe and Whitby, specific methods for the measurement of adren-aline, noradrenalineand its 0-methyl-ated metabolites in tissues were developed. After the intravenous injection of [3H] adrenaline (32) or [3H] noradrenaline (33) in cats, these catecholamines were rapidly and unequally distributed in tissues. The amines were selectively taken up in tissues heavily innervated with sympathetic nerves (heart, spleen). Since negligible amoynts of 3H-labeled catecholamines were present in the brain, a blood brain barrier to these compounds was indicated. 0-Methylated metabolites,[3H] metanephrine and [3H]-normetanephrine, also occurred in tissues. When tissues were examined 2 hours after theadministration of the catecholamines, long after the physio-logical effects had disappeared, they were found to have almost the same levels of [3H] adrenaline and [3H] nor-adrenaline as those found after 2 min-utes).+ These experiments suggested that noradrenaline and adrenaline were taken up and retained in tissues in a-physiologically inactive form. The se-lective binding of the catecholamines by tissues witha high adrenergic innerva-tion pointed to the sympathetic nerves as the sites of retention. To examine this possibility the superior cervical ganglia of cats were removed unilater-ally, and sufficient time (7days) was allowed to elapse for complete degeneration of the sympathetic nerve fibers.[3H] Noradrenaline was then given intra-venously, the animalswere killed 1 hour later, and the [3H] catecholamine