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Brain cortical tissue levels of noradrenaline and its glycol metabolites: effects of ischemia and postischemic administration of idazoxan

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Summary

The brain noradrenaline (NA) system is known to modulate ischemic neuronal damage, and the turnover of NA has been suggested to increase in the early recovery period following cerebral ischemia. Using HPLC and gas chromatography-mass spectrometry we analyzed the tissue levels of NA and its metabolites, 3,4-dihydroxyphenylethyleneglycol (DHPG) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), in rat brain cortex after 10 min of forebrain ischemia followed by 1 h of recirculation. The effect of idazoxan, given in cerebro-pbrotective doses, as a bolus of 0.1 mg·kg-1 immediately after ischemia followed by 10 μg·kg-1·min-1 for 1 h, was also investigated. Ischemia decreased basal NA cortical levels from 384 ng/g tissue in control animals to 214 ng/g, while DHPG increased from 74 to 103 ng/g (+39%) and MHPG from 82 to 154 ng/g (+88%). Conjugated but not free DHPG increased, while both free and conjugated MHPG increased equally. The findings indicate an enhanced postischemic NA turnover with a major proportion of uptake and metabolism occurring extraneuronally, possibly secondary to a saturation of neuronal NA uptake in the postischemic phase. Idazoxan further increased NA turnover, as evidenced by higher postischemic levels of free MHPG and a higher MHPG/NA ratio. A correlation may exist between the protective action of idazoxan and its effect on NA turnover.

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Abbreviations

COMT:

catechol-O-methyltransferase

DHPG:

3,4-dihydroxyphenylethyleneglycol

GC-MS:

gas chromatographymass spectrometry

MHPG:

3-methoxy-4-hydroxyphenylethyleneglycol

NA:

noradrenaline, norepinephrine

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Authors and Affiliations

  1. Laboratory for Experimental Brain Research, University of Lund, Lund University Hospital, S-221 85, Lund, Sweden

    Ingvar Gustafson & Tadeusz Wieloch

  2. Department of Psychiatry and Neurochemistry, University of Lund, Lund University Hospital, S-221 85, Lund, Sweden

    Anders Lidén

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  1. Ingvar Gustafson
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  2. Anders Lidén
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  3. Tadeusz Wieloch
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Gustafson, I., Lidén, A. & Wieloch, T. Brain cortical tissue levels of noradrenaline and its glycol metabolites: effects of ischemia and postischemic administration of idazoxan. Exp Brain Res 90, 551–556 (1992). https://doi.org/10.1007/BF00230938

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  • DOI: https://doi.org/10.1007/BF00230938

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