The kinetic behaviour of [3H]DOPA in living rat brain investigated by compartmental modelling of static autoradiograms

Paul Deep, Hiroto Kuwabara, Albert Gjedde, Paul Cumming

Research output: Contribution to journalArticle

Abstract

The kinetic behaviour of [3H]DOPA in living rat brain was investigated by compartmental modelling of measured activities from combined metabolite pools in a time-series (180 min) of static autoradiograms from right cerebral hemispheres. Two models of [3H]DOPA uptake and metabolism that incorporated the removal of the decarboxylation product, [3H]dopamine, from brain were significantly more accurate than a model in which [3H]dopamine accumulated irreversibly in situ. Present estimates of [3H]DOPA kinetic constants were compared to previously published results based on the analysis of measured activities from individual metabolite pools separated by chromatographic fractionation of [3H]DOPA metabolites in the left cerebral hemispheres of the same rats. Autoradiographic estimates of DOPA decarboxylase activity with respect to [3H]DOPA in brain (k3/(DOPA)) were under-estimated several-fold relative to chromatographic estimates; this discrepancy is explained by post- mortem enzyme activity and omission of biological compartments from the models. However, autoradiographic estimates of the unidirectional blood- brain clearance of [3H]DOPA (K(l)/(DOPA)) and monoamine oxidase activity with respect to [3H]dopamine in brain (k7/(DA)) agreed with chromatographic estimates. This concordance represents the first empirical validation of compartmental modelling of autoradiographic data as a method for quantitatively investigating the kinetic behaviour of radiolabelled L-DOPA in living mammalian brain.

Original languageEnglish (US)
Pages (from-to)157-168
Number of pages12
JournalJournal of Neuroscience Methods
Volume78
Issue number1-2
DOIs
StatePublished - Dec 30 1997

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Keywords

  • Blood-brain clearance
  • Chromatographic fractionation
  • Compartmental model
  • DOPA decarboxylase activity
  • Kinetic constants
  • Rat brain
  • [H]DOPA autoradiography
  • [H]Dopamine

ASJC Scopus subject areas

  • Neuroscience(all)

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