Microdialysis with radiometric monitoring of L-[β-11C]DOPA to assess dopaminergic metabolism: effect of inhibitors of L-amino acid decarboxylase, monoamine oxidase, and catechol-O-methyltransferase on rat striatal dialysate.
The catecholamine, dopamine (DA), is synthesized from 3,4-dihydroxy-L-phenylalanine (L-DOPA) by aromatic L-amino acid decarboxylase (AADC). Dopamine metabolism is regulated by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). To measure dopaminergic metabolism, we used microdialysis with radiometric detection to monitor L-[β-(11)C]DOPA metabolites in the extracellular space of the rat striatum. We also evaluated the effects of AADC, MAO, and COMT inhibitors on metabolite profiles. The major early species measured after administration of L-[β-(11)C]DOPA were [(11)C]3,4-dihydroxyphenylacetic acid ([(11)C]DOPAC) and [(11)C]homovanillic acid ([(11)C]HVA) in a 1:1 ratio, which shifted toward [(11)C]HVA with time. An AADC inhibitor increased the uptake of L-[β-(11)C]DOPA and L-3-O-methyl-[(11)C]DOPA and delayed the accumulation of [(11)C]DOPAC and [(11)C]HVA. The MAO and COMT inhibitors increased the production of [(11)C]3-methoxytyramine and [(11)C]DOPAC, respectively. These results reflect the L-DOPA metabolic pathway, suggesting that this method may be useful for assessing dopaminergic metabolism.
Okada
Maki
M
Molecular Probe Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. mokada@nirs.go.jp
Nakao
Ryuji
R
Hosoi
Rie
R
Zhang
Ming-Rong
MR
Fukumura
Toshimitsu
T
Suzuki
Kazutoshi
K
Inoue
Osamu
O
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology; D001711:Biotransformation; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa; D008297:Male; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D019275:Radiopharmaceuticals; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D001545:Benserazide; D010293:Pargyline; C057726:OR486; D004298:Dopamine; D006719:Homovanillic Acid
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