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标题：3- O -Methyldopa inhibits astrocyte-mediated dopaminergic neuroprotective effects of l -DOPA
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作者：Masato Asanuma ; Ikuko Miyazaki
期刊名称：BMC Neuroscience
印刷版ISSN：1471-2202
电子版ISSN：1471-2202
出版年度：2016
卷号：17
期号：1
页码：1
DOI：10.1186/s12868-016-0289-0
语种：English
出版社：BioMed Central
摘要：Background We evaluated the effects of 3- O -methyldopa (3-OMD), a metabolite of l -DOPA which is formed by catechol- O -methyltransferase (COMT), on the uptake, metabolism, and neuroprotective effects of l -DOPA in striatal astrocytes. We examined changes in the numbers of dopaminergic neurons after treatment with l -DOPA and 3-OMD or entacapone, a peripheral COMT inhibitor, using primary cultured mesencephalic neurons and striatal astrocytes. Results The number of tyrosine hydroxylase-positive dopaminergic neurons was not affected by l -DOPA treatment in mesencephalic neurons alone. However, the increase in viability of dopaminergic neurons in the presence of astrocytes was further enhanced after methyl- l -DOPA treatment (25 µM) in mixed cultured mesencephalic neurons and striatal astrocytes. The neuroprotective effect of 25 µM l -DOPA was almost completely inhibited by simultaneous treatment with 3-OMD (10 or 100 µM), and was enhanced by concomitant treatment with entacapone (0.3 µM). The uptake of l -DOPA into and the release of glutathione from striatal astrocytes after l -DOPA treatment (100 µM) were inhibited by simultaneous exposure to 3-OMD (100 µM). Conclusions These data suggest that l -DOPA exerts its neuroprotective effect on dopaminergic neurons via astrocytes and that 3-OMD competes with l -DOPA by acting on target molecule(s) (possibly including glutathione) released from astrocytes. Since some amount of entacapone can cross the blood–brain barrier, this reagent may enhance l -DOPA transportation by inhibiting COMT and increase the astrocyte-mediated neuroprotective effects of l -DOPA on dopaminergic neurons.
关键词：Astrocyte ; l ;-DOPA ; 3- O -Methyldopa ; Glutathione ; Entacapone