Acute neuroleptic stimulates DOPA decarboxylase in porcine brain in vivo.
The activity of DOPA decarboxylase measured in homogenates from rat striatum, or calculated from the rate of tracer decarboxylation measured ex vivo, is stimulated following acute treatment with antagonists of dopamine D2-like receptors. We used compartmental kinetics to test the hypothesis that utilization of the DOPA decarboxylase substrate [(18)F]fluorodopa is potentiated in living striatum following acute treatment with a typical neuroleptic. The kinetics of the tracer uptake were determined in eight anesthetized female pigs (40 kg) and in three animals receiving an infusion of haloperidol (75 microg kg(-1) h(-1)) for 1 h prior to tracer administration and throughout the 2-h positron emission recording. The relative activity of DOPA decarboxylase in striatum was increased threefold by the treatment. This potentiation of DOPA decarboxylation after pharmacological blockade of dopamine D2-like receptors may be used to optimize the utilization of exogenous DOPA in the treatment of Parkinson's disease.
Danielsen
E H
EH
PET Center, Arhus Kommunehospital, Arhus, Denmark.
Smith
D
D
Hermansen
F
F
Gjedde
A
A
Cumming
P
P
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D004296:Dopa Decarboxylase / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D065127:Dopamine D2 Receptor Antagonists; D004334:Drug Administration Schedule; D005260:Female; D006220:Haloperidol / Q000493:pharmacokinetics; D017072:Neostriatum / Q000187:drug effects* / Q000201:enzymology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D010300:Parkinson Disease / Q000188:drug therapy; D010599:Pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013552:Swine; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase; D006220:Haloperidol; D004298:Dopamine