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Intracerebrally administered (6r)-l-erythro-tetrahydrobiopterin does not affect extracellular levels of dopamine and serotonin metabolites in rat striatum in vivo during measurement by brain micro-dialysis system
Institution:1. Nagoya University College of Medical Technology, Nagoya 461, Japan;2. Department of Psychiatry, Nagoya University School of Medicine, Nagoya 466, Japan;3. Department of Biochemistry, Nagoya University School of Medicine, Nagoya 466, Japan;1. Department of Ophthalmology, Guangzhou First People''s Hospital, Guangzhou Medical University, Second Affiliated Hospital of South China University of Technology, Guangzhou, 510080, China;2. Departments of Anesthesia and Pain Medicine, Guangzhou First People''s Hospital, Guangzhou Medical University, Second Affiliated Hospital of South China University of Technology, Guangzhou, 510080, China;1. Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany;2. Center for Rare Diseases, University of Leipzig Medical Center, Leipzig, Germany;3. Department of Epilepsy Genetics and Personalized Treatment, The Danish Epilepsy Centre, Dianalund, Denmark;4. Department of Regional Health Research, University of Southern Denmark, Odense, Denmark;5. Applied&Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium;6. Translational Neurosciences, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium;7. Department of Neurology, Antwerp University Hospital, Antwerp, Belgium;8. Folkhälsan Research Center, Helsinki, Finland;9. Hospital for Children and Adolescents, Department of Women and Child Health, University of Leipzig Medical Center, Leipzig, Germany;10. Division of Paediatric Epileptology, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;1. Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan;2. Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan;3. Department of Innovative Seeds Evaluation, National Cancer Center Research Institute, Tokyo, Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan;1. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China;2. National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China;3. Shenzhen Key Laboratory for Anti-ageing and Regenerative Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, PR China;4. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, PR China;1. Division of Pediatric General and Thoracic Surgery, Cincinnati Children?s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, Ohio 45229;2. Department of Surgery, Brody School of Medicine, East Carolina University, Greenville, North Carolina
Abstract:By the use of the brain micro-dialysis technique combined with HPLC, the changes in the extracellular levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and a serotonin(5-HT) metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were examined in the rat striatum before and after intracerebral injection of a vehicle or (6R)-l-erythro-tetrahydrobiopterin (6R-BH4), the natural form of the cofactor for the tryrosine hydroxylase and tryptophan hydroxylase. No apparent change after the 6R-BH, treatment was found in the levels of DA, DOPAC, HVA and 5-HIAA in the striatal dialysate. In contrast, the levels of total biopterin in both the operated (dialysis probe-implanted) and unoperated striatum of 6R-BH4-treated rats increased by 23- and 93-fold, respectively, when compared with those of the control, vehicle-treated rats. The results indicate that increased levels of the tetrahydrobiopterin cofactor may not affect the release of DA and the extracellular level of DA and 5-HT metabolites in the physiologically normal brain.
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