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Brain Dialysis: In Vivo Metabolism of Dopamine and Serotonin by Monoamine Oxidase A but Not B in the Striatum of Unrestrained Rats
Author(s) -
Kato Takeshi,
Dong Bei,
Ishii Kayoko,
Kinemuchi Hiroyasu
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb00650.x
Subject(s) - pargyline , homovanillic acid , monoamine oxidase , chemistry , dopamine , endocrinology , serotonin , metabolite , clorgyline , medicine , 3,4 dihydroxyphenylacetic acid , monoamine neurotransmitter , striatum , monoamine oxidase b , pharmacology , biochemistry , biology , enzyme , receptor
A dialysis cannula was implanted into rat striatum while the animals were anesthetized, and the area was perfused with Ringer solution while the animals were unanesthetized after at least 3 days following surgery. Concentrations of the metabolites of 3,4‐dihydroxy‐phenylethylamine (DA) and 5‐hydroxytryptamine (5‐HT) in the perfusate were determined by HPLC with electrochemical detection. Levels of the DA metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perfusate significantly decreased after pargyline administration (50 mg/kg i.p.), which may inhibit not only monoamine oxidase (MAO)‐B but also MAO‐A in these high doses. The level of the 5‐HT metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) also decreased after pargyline treatment, although change in the relative level of 5‐HIAA was less than that of DOPAC or HVA. To clarify the mechanisms for the metabolism of monoamines in rat striatum, highly specific MAO‐A and ‐B inhibitors were used in the following experiments. Treatment with l ‐deprenyl (10 mg/kg), a specific inhibitor for MAO‐B, did not cause any statistically significant change in DOPAC, HVA, and 5‐HIAA levels. No significant change was found in rat striatal homogenates at 2 h after the same treatment with l ‐deprenyl. In contrast, low‐dose treatment (1 mg/kg) with clorgyline, a specific inhibitor for MAO‐A, caused a significant decrease in levels of these three metabolites in both the perfusates and tissue homogenates. In addition to the above three metabolites, the level of 3‐methoxytyramine, which is an indicator of the amount of DA released, greatly increased after treatment with a low dose (1 mg/kg) of clorgyline. These results suggest that DA and 5‐HT in rat striatum may be preferentially deaminated by MAO‐A in vivo.