[3H]DOPA formed from [3H]tyrosine in living rat brain is not committed to dopamine synthesis

Paul Cumming, Ariel Ase, Hiroto Kuwabara, Albert Gjedde

Research output: Contribution to journalArticle

Abstract

Tyrosine hydroxylase of catecholamine neurons catalyzes the synthesis of 3,4-dihydroxphenylalanine (DOPA), which is subsequently metabolized to dopamine by DOPA decarboxylase (DDC). However, DOPA is not committed to decarboxylation in vivo because export of DOPA from brain and metabolism of DOPA other than decarboxylation are possible. To estimate the relative magnitudes of the several fates of DOPA, the kinetics of the uptake and metabolism of L-[3H]tyrosine ([3H]Tyr, intravenous infusion) was measured in brain of rats pretreated with NSD 1015, an inhibitor of DDC. Some rats were pretreated with haloperidol before the blockade of DDC. The [3H]Tyr was incorporated into brain protein at a rate constant of 0.03 min-1. The relative tyrosine hydroxylase activity in striatum was 0.005 min-1 at 30 minutes after NSD 1015, 0.011 min-1 3 hours later, and 0.020 min-1 after haloperidol treatment. The rate constant for the clearance of DOPA from brain (0.06 min-1) and earlier estimates of the rate constant of DDC activity in striatum (0.26 min-1) together predict that 80% of DOPA formed in normal rat striatum normally is available for dopamine synthesis. It follows that modulation of DDC activity can influence the rate of DA synthesis by affecting the relative magnitude of the several fates of DOPA in living brain.

Original languageEnglish (US)
Pages (from-to)491-499
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume18
Issue number5
DOIs
StatePublished - May 1998

Keywords

  • DOPA
  • DOPA decarboxylase
  • Dopamine
  • Haloperidol
  • Metabolism
  • NSD 1015
  • Protein synthesis
  • Striatum
  • Tyrosine
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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