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大鼠脑中结合儿茶酚胺的生化及药理学特性

Biochemical and pharmacological characteristics of conjugated catecholamines in the rat brain.

作者信息

Karoum F, Chuang L W, Wyatt R J

出版信息

J Neurochem. 1983 Jun;40(6):1735-41. doi: 10.1111/j.1471-4159.1983.tb08149.x.

Abstract

Mass-fragmentographic methods are described that enable the simultaneous measurement of total, free, and conjugated catecholamines in brain tissues. These methods were used to assess the distribution, kinetics, and pharmacological characteristics of total, free, and conjugated catecholamines in the hypothalamus, caudate nucleus, hippocampus, and septum. Conjugated norepinephrine (NE) represents approximately 20% of total NE in the hypothalamus, septum, and hippocampus, whereas the percentage is approximately 50% in the caudate nucleus. The percentages of conjugated dopamine (DA) in these brain areas are consistently less than those of NE (approximately 13%). Although in the hypothalamus the steady-state concentrations of total, free, and conjugated NE are over four times higher than those of the corresponding total, free, and conjugated DA, the turnover rates of this DA are comparable with those of the corresponding NE. Further, the ratios of conjugated NE or DA turnover rates to those of the total amines are higher than the corresponding ratios of their steady-state concentrations. Treatments with pargyline (75 mg/kg, i.p.; rats killed 30 and 60 min later) failed to change the contents of conjugated catecholamines in the hypothalamus and the caudate nucleus significantly. Pharmacological manipulation with a number of prototypic drugs revealed that although the assay of conjugated catecholamines might shed additional light on the effects of drugs on central catecholamines, the assessment of total or free amines are on the whole equally informative. In conclusion, a detailed assessment of brain conjugated catecholamines is reported. The information provided, fills a gap in our knowledge that has up to now not been adequately addressed.

摘要

本文描述了能够同时测量脑组织中总儿茶酚胺、游离儿茶酚胺和结合儿茶酚胺的质量碎片谱法。这些方法用于评估下丘脑、尾状核、海马体和隔区中总儿茶酚胺、游离儿茶酚胺和结合儿茶酚胺的分布、动力学和药理学特征。结合去甲肾上腺素(NE)约占下丘脑、隔区和海马体中总NE的20%,而在尾状核中这一比例约为50%。这些脑区中结合多巴胺(DA)的百分比始终低于NE的百分比(约13%)。虽然在下丘脑中,总NE、游离NE和结合NE的稳态浓度比相应的总DA、游离DA和结合DA高出四倍多,但这种DA的周转率与相应的NE相当。此外,结合NE或DA的周转率与总胺周转率的比值高于它们稳态浓度的相应比值。用帕吉林(75mg/kg,腹腔注射;30分钟和60分钟后处死大鼠)处理未能显著改变下丘脑和尾状核中结合儿茶酚胺的含量。用多种原型药物进行药理学操作表明,虽然结合儿茶酚胺的测定可能会为药物对中枢儿茶酚胺的作用提供更多信息,但总体而言,总胺或游离胺的评估同样具有参考价值。总之,本文报道了对脑结合儿茶酚胺的详细评估。所提供的信息填补了我们目前尚未充分解决的知识空白。

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