(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.
In an attempt to monitor μm-level trace constituents, we applied here (1)H-{(13)C-(15)N} triple-resonance nuclear magnetic resonance (NMR) to (13)C/(15)N-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 (13)C/(15)N-enrichment is synthetically accessible.
Advanced Biomedical Engineering Research Unit Center for the Promotion of Interdisciplinary Education and Research Kyoto University, Katsura, Nishikyo-ku Kyoto 615-8510 Japan; Department of Life Systems Institute of Technology and Science Graduate School Tokushima University Tokushima 770-8506 Japan.
Hisatsugu
H
Yamada
Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering Kyoto University, Katsura, Nishikyo-ku Kyoto 615-8510 Japan.
Tetsuro
T
Kameda
Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering Kyoto University, Katsura, Nishikyo-ku Kyoto 615-8510 Japan; Research and Educational Unit of Leaders for Integrated Medical System Center for the Promotion of Interdisciplinary Education and Research Kyoto University, Katsura, Nishikyo-ku Kyoto 615-8510 Japan.
Yu
Y
Kimura
Department of Systems Science Graduate School of Informatics Kyoto University, Yoshida-honmachi, Sakyo-ku Kyoto 606-8501 Japan.
Hirohiko
H
Imai
Department of Systems Science Graduate School of Informatics Kyoto University, Yoshida-honmachi, Sakyo-ku Kyoto 606-8501 Japan.
Tetsuya
T
Matsuda
Department of Chemistry and Biotechnology The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku Tokyo 113-8656 Japan.
Shinsuke
S
Sando
Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering Kyoto University, Katsura, Nishikyo-ku Kyoto 615-8510 Japan; Division of Multidisciplinary Chemistry Institute for Chemical Research Kyoto University, Gokanosho, Uji Kyoto 611-0011 Japan.
Akio
A
Toshimitsu
Kyoto University, Katsura, Nishikyo-ku Kyoto 615-8510 Japan.
Yasuhiro
Y
Aoyama
Advanced Biomedical Engineering Research Unit Center for the Promotion of Interdisciplinary Education and Research Kyoto University, Katsura, Nishikyo-ku Kyoto 615-8510 Japan; Department of Energy and Hydrocarbon Chemistry Graduate School of Engineering Kyoto University, Katsura, Nishikyo-ku Kyoto 615-8510 Japan.
Teruyuki
T
Kondo
L-dopa; dopamine; metabolic analysis; neurotransmitters; stable isotope enrichment; triple-resonance NMR