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 | Zendy

Maki Okada | Zendy; Ryuji Nakao | Zendy; Rie Hosoi | Zendy; MingRong Zhang | Zendy; Toshimitsu Fukumura | Zendy; Kazutoshi Suzuki | Zendy; Osamu Inoue | Zendy

Open Access

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

Author(s) -

Maki Okada,

Ryuji Nakao,

Rie Hosoi,

MingRong Zhang,

Toshimitsu Fukumura,

Kazutoshi Suzuki,

Osamu Inoue

Publication year - 2010

Publication title -

journal of cerebral blood flow and metabolism

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.167

H-Index - 193

eISSN - 1559-7016

pISSN - 0271-678X

DOI - 10.1038/jcbfm.2010.58

Subject(s) - catechol o methyl transferase , monoamine oxidase , dopaminergic , monoamine oxidase b , biochemistry , microdialysis , aromatic l amino acid decarboxylase , d amino acid oxidase , chemistry , dopamine , metabolism , catechol , 3,4 dihydroxyphenylacetic acid , enzyme , oxidase test , homovanillic acid , biology , endocrinology , serotonin , genotype , extracellular , receptor , gene

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.

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