(13)C/(15)N-Enriched l-Dopa as a Triple-Resonance NMR Probe to Monitor Neurotransmitter Dopamine in the Brain and Liver Extracts of Mice.
(13)C/(15)N-Enriched l-Dopa as a Triple-Resonance NMR Probe to Monitor Neurotransmitter Dopamine in the Brain and Liver Extracts of Mice.
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DOI：
10.1002/open.201500196
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发表时间：
2016-04
期刊：
影响因子：
2.3
通讯作者：
Kondo T
中科院分区：
文献类型：
--
作者：
Yamada H;Kameda T;Kimura Y;Imai H;Matsuda T;Sando S;Toshimitsu A;Aoyama Y;Kondo T
为了监测微米级的痕量成分，我们在这里将 1H-{13C-15N} 三重共振核磁共振 (NMR) 应用于富含 13C/15N 的左旋多巴，作为大脑中神经递质多巴胺的不可避免的前体。三重共振的完美选择性（使内源性成分沉默）和μm级灵敏度（配备低温探针的700 MHz光谱仪）允许对小鼠大脑和肝脏中施用的左旋多巴/多巴胺进行明确和定量的代谢和药代动力学分析。大脑中产生的多巴胺水平（在7-76 μm范围内，涵盖了〜30 μm的典型刺激水平）可以在体外清晰地监测，但略低于小动物7 T MR机器的检测限。这项工作表明，微米级痕量成分是离体监测的潜在目标，只要它们含有 N 原子，并且它们适当的 13C/15N 富集是可合成的。
In an attempt to monitor μm‐level trace constituents, we applied here 1H‐{13C‐15N} triple‐resonance nuclear magnetic resonance (NMR) to 13C/15N‐enriched l‐Dopa as the inevitable precursor of the neurotransmitter dopamine in the brain. The perfect selectivity (to render endogenous components silent) and μm‐level sensitivity (700 MHz spectrometer equipped with a cryogenic probe) of triple‐resonance allowed the unambiguous and quantitative metabolic and pharmacokinetic analyses of administered l‐Dopa/dopamine in the brain and liver of mice. The level of dopamine generated in the brain (within the range 7–76 μm, which covers the typical stimulated level of ∼30 μm) could be clearly monitored ex vivo, but was slightly short of the detection limit of a 7 T MR machine for small animals. This work suggests that μm‐level trace constituents are potential targets of ex vivo monitoring as long as they contain N atom(s) and their appropriate 13C/15N‐enrichment is synthetically accessible.