Gordon J H, Shellenberger M K
Res Commun Chem Pathol Pharmacol. 1977 Jan;16(1):33-46.
The means by which the brain handles the dopamine (DA) metabolite, 3-methoxytyramine (3-MT), has not been characterized. This study has examined one aspect by utilizing tritiated 3-MT in synaptosomes from rat striatum and slices of both striatum and cerebellum. No accumulation of 3-MT could be demonstrated in synaptosomes but DA (0.1 muM) uptake was inhibited by 3-MT (IC50 = 1.3 X 10(-5)M). Studies in brain tissue slices showed: 1) 3-MT accumulation was greater than could be expected from diffusion at a high concentration (10 muM) of amine; 2) the accumulated amine was easily washed out of the tissue slice; 3) the uptake appeared to be saturable with high estimated values for Km and Vmax; and 4) agents, such as metanephrine, which inhibit peripheral extraneuronal amine uptake had similar effectiveness against 3-MT uptake. It was concluded that: 1) the mechanism for the accumulation of 3-MT is similar in structurally different areas of the brain; 2) 3-MT is accumulated by a mechanism which is not a part of the nerve terminal; and 3) 3-MT accumulation in the brain is similar to the extraneuronal accumulation of amines in the periphery.
大脑处理多巴胺(DA)代谢物3 - 甲氧基酪胺(3 - MT)的方式尚未明确。本研究通过在大鼠纹状体的突触体以及纹状体和小脑切片中使用氚标记的3 - MT,对其中一个方面进行了研究。在突触体中未发现3 - MT的积累,但3 - MT(IC50 = 1.3×10⁻⁵M)抑制了DA(0.1μM)的摄取。脑组织切片研究表明:1)在高浓度(10μM)胺的情况下,3 - MT的积累大于扩散所能预期的量;2)积累的胺很容易从组织切片中洗出;3)摄取似乎是可饱和的,Km和Vmax的估计值较高;4)抑制外周非神经元胺摄取的药物,如间甲肾上腺素,对3 - MT摄取具有相似的抑制效果。得出的结论是:1)大脑结构不同区域中3 - MT积累的机制相似;2)3 - MT通过一种并非神经末梢一部分的机制积累;3)大脑中3 - MT的积累类似于外周胺的非神经元积累。