Bioactive 6-nitronorepinephrine identified in mammalian brain

Futoshi Shintani, Takeshi Kinoshita, Shigenobu Kanba, Tomio Ishikawa, Eiji Suzuki, Nobuyuki Sasakawa, Ryuichi Kato, Masahiro Asai, Toshio Nakaki

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Abstract

Norepinephrine (NE) (von Euler, U.S. (1972) in Catecholamines (Blaschko, H., and Muscholl, E., eds.) pp. 186-230, Springer-Verlag, Berlin) and nitric oxide (NO·) function as neurotransmitters in the nervous system. We have shown that NE levels in the rat hypothalamic paraventricular nucleus (Shintani, F., Kato, R., Kinoshita, N., Kanba, S., Asai, M., and Nakaki, T. (1995) Proceedings of the Satellite Symposium, 4th IBRO World Congress on Neuroscience, Otsu, 1995) diminish in the presence of NO·. This observation prompted us to explore the possibility of an in vivo interaction between NE and NO· or NO·-related molecules. In fact, nitration of NE has been shown to occur in vitro (d'Ischia, M., and Costantini, C. (1995) Bioorg. Med. Chem. 3, 923-927). We now report the identification of 6-nitronorepinephrine in the mammalian brain. Amounts of 6-nitronorepinephrine in the rat brain were attenuated by intraperitoneal administration of an inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (L-NAME). This was reversed by coadministration of L-arginine, suggesting that nitric oxide synthase participated in the formation of 6-nitronorepinephrine. Moreover, we found that 6-nitronorepinephrine inhibits the activity of catechol O- methyltransferase, as well as NE transport into rat synaptosomes. A rat brain microdialysis experiment showed that perfusion of 6-nitronorepinephrine into the rat paraventricular nucleus significantly elevated NE while decreasing 3- methoxy-4-hydroxyphenylglycol and that L-NAME administered intraperitoneally decreased NE and increased 3-methoxy-4-hydroxyphenylglycol. These observations suggest that 6-nitronorepinephrine generated in nuclei containing both adrenergic and nitrergic neurons inhibits NE inactivation. We propose that 6-nitronorepinephrine is a potential signal molecule linking the actions of NE and NO·.

Original languageEnglish
Pages (from-to)13561-13565
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number23
DOIs
Publication statusPublished - Jun 25 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Shintani, F., Kinoshita, T., Kanba, S., Ishikawa, T., Suzuki, E., Sasakawa, N., Kato, R., Asai, M., & Nakaki, T. (1996). Bioactive 6-nitronorepinephrine identified in mammalian brain. Journal of Biological Chemistry, 271(23), 13561-13565. https://doi.org/10.1074/jbc.271.23.13561