Striatal dopamine metabolism in monoamine oxidase B-deficient mice: A brain dialysis study

被引:67
作者
Fornai, F
Chen, K
Giorgi, FS
Gesi, M
Alessandri, MG
Shih, JC
机构
[1] Univ So Calif, Pharmaceut Sci Ctr, Dept Mol Pharmacol & Toxicol, Sch Pharm, Los Angeles, CA 90033 USA
[2] Univ Pisa, Dept Human Morphol & Appl Biol, Pisa, Italy
[3] Univ Pisa, IRCCS Stella Maris, INPE, Pisa, Italy
[4] INM Neuromed, Pozzilli, Italy
[5] Univ So Calif, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA USA
关键词
brain dialysis; L-DOPA; dopamine; monoamine oxidase B knock-out mice monoamine oxidase;
D O I
10.1046/j.1471-4159.1999.0732434.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have studied striatal dopamine (DA) metabolism in monoamine oxidase (MAO) B-deficient mice using brain microdialysis. Baseline DA levels were similar in wild-type and knock-out (KO) mice. Administration of a selective MAO A inhibitor, clorgyline (2 mg/kg), increased DA levels and decreased levels of its metabolites in all mice, but a selective MAO B inhibitor, I-deprenyl (1 mg/kg), had no effect. Administration of 10 and 50 mg/kg L-DOPA, the precursor of DA, increased the levels of DA similarly in wild-type and KO mice. The highest dose of L-DOPA (100 mg/kg) produced a larger increase in DA in KO than wild-type mice. This difference was abolished by pretreating wild-type mice with /-deprenyl. These results suggest that in mice, DA is only metabolized by MAO A under basal conditions and by both MAO A and B at high concentrations. This is in contrast to the rat, where DA is always metabolized by MAO A regardless of concentration.
引用
收藏
页码:2434 / 2440
页数:7
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