Effects of aldehyde/aldose reductase inhibition on neuronal metabolism of norepinephrine

Minoru Kawamura, Irwin J. Kopin, Peter F. Kador, Sanai Sato, Olga Tjurmina, Graeme Eisenhofer

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

After norepinephrine (NE) is deaminated by monoamine oxidase (MAO), the aldehyde formed is either metabolized to 3,4-dihydroxymandelic acid (DHMA) by aldehyde dehydrogenase or is converted to 3,4-dihydroxyphenylglycol (DHPG) by aldehyde or aldose reductase. The present study examined the effects of inhibition of aldehyde and aldose reductase on production of DHPG and DHMA in rats. Mean (± S.E.) baseline plasma concentrations of DHPG (4.73 ± 0.21 pmol/ml) were 60-fold higher than those of DHMA 0.08 ± 0.01 pmol/ml). Inhibition of aldose and aldehyde reductase reduced plasma DHPG concentrations to 1.88 ± 0.14 pmol/ml and increased plasma DHMA to 4.43 ± 0.29 pmol/ml; additional inhibition of MAO reduced plasma DHPG to 0.16 ± 0.06 pmol/ml and DHMA to 0.19 ± 0.02 pmol/ml. Inhibition of aldehyde and aldose reductase also increased brain tissue levels of DHMA from 8 ± 2 to 384 ± 47 pmol/g and decreased levels of DHPG from 70 ± 9 to 44 ± 5 pmol/g. The results show that DHMA is normally a minor metabolite of NE, but becomes a major metabolite after aldehyde/aldose reductase inhibition.

Original languageEnglish (US)
Pages (from-to)145-148
Number of pages4
JournalJournal of the Autonomic Nervous System
Volume66
Issue number3
DOIs
StatePublished - Oct 13 1997

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Keywords

  • 3,4-Dihydroxymandelic acid
  • 3,4-Dihydroxyphenylglycol
  • Aldehyde reductase
  • Monoamine oxidase
  • Norepinephrine
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Clinical Neurology

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