Effect of intracerebral 6-nitronoradrenaline, an endogenous catechol-O-methyltransferase (COMT) inhibitor, on striatal dopamine metabolism in anaesthetised rats

M. Huotari, M. Passlin, H. L. Nordberg, M. Forsberg, S. Kotisaari, L. Tuomisto, F. Shintani, Kenji Tanaka, I. Reenilä, K. Laitinen, P. T. Männistö

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

6-Nitronoradrenaline, a bioactive compound recently identified in the brain, is known to inhibit catechol-O-methyltransferase. To study its effect on dopamine metabolism, it was administered into rat striatum via a microdialysis probe. Other nitrated catechols (6-nitrodopamine, 6-nitro-DOPAC and 5-nitro-HVA) were studied for comparison. Tolcapone, a selective catechol-O-methyltransferase inhibitor, was used as a positive reference compound. Both 6-nitronoradrenaline and tolcapone increased striatal extracellular dopamine levels during the perfusion (at 100 μM concentration but not at 10 μM) and decreased the efflux of homovanillic acid. Tolcapone, but not other nitrated catechols, increased 3,4-dihydroxyphenylacetic acid efflux. None of the compounds inhibited MAO-B activity at 100 μM or lower. At 1 mM, 6-nitrodopamine inhibited MAO-B by 60%. Compared to tolcapone, other nitrated catechols were very weak COMT inhibitors in vitro. Neither tolcapone nor 6-nitronoradrenaline modified the metabolism of L-dopa which was given peripherally. In binding studies, both 6-nitronoradrenaline and other nitrocatechols failed to affect the dopamine transporter even at high μmolar concentrations. In conclusion, exogenous 6-nitronoradrenaline can act as a COMT inhibitor in the striatum and elevate striatal dopamine levels without inhibiting dopamine reuptake. Whether endogenous 6-nitronoradrenaline can be formed also in vivo in the striatum and act as a regulator of dopaminergic tone remains to be determined

Original languageEnglish
Pages (from-to)47-52
Number of pages6
JournalJournal of Neuroscience Methods
Volume109
Issue number1
DOIs
Publication statusPublished - 2001 Aug 15
Externally publishedYes

Fingerprint

Corpus Striatum
Catechols
Dopamine
3,4-Dihydroxyphenylacetic Acid
Monoamine Oxidase
Catechol O-Methyltransferase
Homovanillic Acid
Dopamine Plasma Membrane Transport Proteins
Microdialysis
Levodopa
Perfusion
Catechol O-Methyltransferase Inhibitors
tolcapone
Brain

Keywords

  • 6-Nitrodopamine
  • 6-Nitronoradrenaline
  • Brain microdialysis
  • COMT inhibition
  • Dopamine reuptake
  • Tolcapone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effect of intracerebral 6-nitronoradrenaline, an endogenous catechol-O-methyltransferase (COMT) inhibitor, on striatal dopamine metabolism in anaesthetised rats. / Huotari, M.; Passlin, M.; Nordberg, H. L.; Forsberg, M.; Kotisaari, S.; Tuomisto, L.; Shintani, F.; Tanaka, Kenji; Reenilä, I.; Laitinen, K.; Männistö, P. T.

In: Journal of Neuroscience Methods, Vol. 109, No. 1, 15.08.2001, p. 47-52.

Research output: Contribution to journalArticle

Huotari, M, Passlin, M, Nordberg, HL, Forsberg, M, Kotisaari, S, Tuomisto, L, Shintani, F, Tanaka, K, Reenilä, I, Laitinen, K & Männistö, PT 2001, 'Effect of intracerebral 6-nitronoradrenaline, an endogenous catechol-O-methyltransferase (COMT) inhibitor, on striatal dopamine metabolism in anaesthetised rats', Journal of Neuroscience Methods, vol. 109, no. 1, pp. 47-52. https://doi.org/10.1016/S0165-0270(01)00400-9
Huotari, M. ; Passlin, M. ; Nordberg, H. L. ; Forsberg, M. ; Kotisaari, S. ; Tuomisto, L. ; Shintani, F. ; Tanaka, Kenji ; Reenilä, I. ; Laitinen, K. ; Männistö, P. T. / Effect of intracerebral 6-nitronoradrenaline, an endogenous catechol-O-methyltransferase (COMT) inhibitor, on striatal dopamine metabolism in anaesthetised rats. In: Journal of Neuroscience Methods. 2001 ; Vol. 109, No. 1. pp. 47-52.
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abstract = "6-Nitronoradrenaline, a bioactive compound recently identified in the brain, is known to inhibit catechol-O-methyltransferase. To study its effect on dopamine metabolism, it was administered into rat striatum via a microdialysis probe. Other nitrated catechols (6-nitrodopamine, 6-nitro-DOPAC and 5-nitro-HVA) were studied for comparison. Tolcapone, a selective catechol-O-methyltransferase inhibitor, was used as a positive reference compound. Both 6-nitronoradrenaline and tolcapone increased striatal extracellular dopamine levels during the perfusion (at 100 μM concentration but not at 10 μM) and decreased the efflux of homovanillic acid. Tolcapone, but not other nitrated catechols, increased 3,4-dihydroxyphenylacetic acid efflux. None of the compounds inhibited MAO-B activity at 100 μM or lower. At 1 mM, 6-nitrodopamine inhibited MAO-B by 60{\%}. Compared to tolcapone, other nitrated catechols were very weak COMT inhibitors in vitro. Neither tolcapone nor 6-nitronoradrenaline modified the metabolism of L-dopa which was given peripherally. In binding studies, both 6-nitronoradrenaline and other nitrocatechols failed to affect the dopamine transporter even at high μmolar concentrations. In conclusion, exogenous 6-nitronoradrenaline can act as a COMT inhibitor in the striatum and elevate striatal dopamine levels without inhibiting dopamine reuptake. Whether endogenous 6-nitronoradrenaline can be formed also in vivo in the striatum and act as a regulator of dopaminergic tone remains to be determined",
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AU - Forsberg, M.

AU - Kotisaari, S.

AU - Tuomisto, L.

AU - Shintani, F.

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