In vivo regulation of DOPA decarboxylase by dopamine receptors in rat brain.

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To test the hypothesis that dopamine (DA) receptors influence cerebral DOPA-decarboxylase (DDC) activity in vivo, we used HPLC to measure the kinetics of the cerebral uptake and metabolism of [3H]DOPA in carbidopa-treated rats, and in rats also treated acutely with a DA receptor antagonist (flupenthixol, 2 mg/kg, intraperitoneally) or a DA receptor agonist (apomorphine, 200 microg/g, subcutaneously). The unidirectional blood-brain clearance of [3H]DOPA (K1DOPA, 0.030 mL g(-1) min(-1)) increased by 50% after flupenthixol. The magnitudes of the relative DDC activity (k3DOPA) in striatum (0.20 min(-1)), olfactory tubercle (0.11 min(-1)), and hypothalamus (0.15 min(-1)) of carbidopa-treated rats were doubled with flupenthixol, but cortical DDC activity was unaffected (0.02 min(-1)). Apomorphine reduced the magnitude of k3DOPA in striatum by 20%. The rate constant for catabolism of [3H]DA formed in brain (k7', monoamine oxidase [MAO] activity), which ranged from 0.025 min(-1) in striatum to 0.08 min(-1) in hypothalamus of carbidopa-treated rats, globally increased 2- to 4-fold after flupenthixol, and decreased to 0.003 min(-1) in striatum after apomorphine. These in vivo results confirm the claim that acute blockade of DA receptors with flupenthixol stimulates the synthesis of [3H]DA from [3H]DOPA, and that this [3H]DA is subject to accelerated catabolism. Conversely, activation of the DA receptors with apomorphine inhibits DDC activity and DA catabolism.
Original languageEnglish
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number11
Pages (from-to)1254-60
Number of pages6
Publication statusPublished - 1997
Externally publishedYes

ID: 14944974