6R-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN AS A REGULATOR OF DOPAMINE AND SEROTONIN BIOSYNTHESIS IN THE RAT-BRAIN
6R-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN AS A REGULATOR OF DOPAMINE AND SEROTONIN BIOSYNTHESIS IN THE RAT-BRAIN
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DOI：
10.1016/0003-9861(85)90831-8
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发表时间：
1985-01-01
影响因子：
3.9
通讯作者：
HAYAISHI, O
中科院分区：
文献类型：
--
作者：
MIWA, S;WATANABE, Y;HAYAISHI, O
以7，8-二氢生物蝶呤为原料，利用二氢叶酸还原酶合成了四氢生物蝶呤的天然异构体6 R-L-赤型四氢生物蝶呤（6 R-BH 4）。通过测定NSD 1015 [富马酸3-羟基苄肼]抑制芳香族L-氨基酸脱羧酶后多巴和5-羟色氨酸（5-HTP）的蓄积量以及多巴胺（DA）和5-羟色胺（5-HT）代谢产物的含量，研究了侧脑室注射6 R-BH_4对大鼠脑内单胺类神经递质生物合成的影响。多巴和5-HTP的形成在注射后增加，在约0.5时达到最大水平。注射6 R-BH 4后，多巴和5-HTP的形成在全脑中剂量依赖性地增加，并且当剂量> 300 μ g/大鼠时达到平台。多巴和5-HTP的增强分别为100%和70%。4个脑区的多巴和5-羟色胺合成增加，但不同脑区的刺激程度不同。注射6 R-BH_4后，各脑区DA和5-HT代谢产物含量均增加，尤其是间脑和脑干。注射6 R-BH_4后DA和5-HT含量略有升高。6 R-BH_4浓度在DA和5-HT神经元内可能是次最大的，并且脑中6 R-BH_4的增加增强DA和5-HT的生物合成。
6R-L-Erythro-tetrahydrobiopterin (6R-BH4), the natural isomer of tetrahydrobiopterin, was synthesized from 7,8-dihydrobiopterin using dihydrofolate reductase. The effects of intracerebroventricular injection of 6R-BH4 on the biosyntheses of neurotransmitter monoamines in the rat brain were investigated by measuring accumulation of dopa and 5-hydroxytryptophan (5-HTP) after the inhibition of aromatic L-amino acid decarboxylase by NSD 1015 [3-hydroxybenzylhydrazine fumarate] and the contents of metabolites of dopamine (DA) and 5-hydroxytryptamine (5-HT). The formation of dopa and 5-HTP increased after the injection, reached a maximum level at .apprx. 1 h, then leveled off and reached a plateau over 2 h up to 8 h.The formation of dopa and 5-HTP increased dose-dependently in the whole brain after the injection of 6R-BH4, and reached a plateau when the dose was > 300 .mu.g/rat. The enhancement was 100 and 70% for dopa and 5-HTP, respectively. The formation of dopa and 5-HTP increased in 4 brain regions, but the degree of stimulation was different among the brain regions. The contents of DA and 5-HT metabolites increased after the injection of 6R-BH4 in all brain regions tested, especially in the diencephalon and brain stem. The contents of DA and 5-HT increased slightly after the injection of 6R-BH4. 6R-BH4 concentration may be submaximal within DA and 5-HT neurons, and that an increase in 6R-BH4 in the brain enhances the biosyntheses of DA and 5-HT.