Peripherally administered tetrahydrobiopterin increases in vivo tryptophan hydroxylase activity in the striatum after transplantation of fetal ventral mesencephalon in six hydroxydopamine lesioned rats.
The intraperitoneal administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), a natural cofactor for tyrosine hydroxylase and tryptophan hydroxylase (TRH), dose-dependently increased the extracellular concentration of 6R-BH4 itself in rat striatum. The concentration was investigated by in vivo microdialysis and measured simultaneously with 5-hydroxytryptophan (5-HTP), a precursor of serotonin, by high performance liquid chromatography with electrochemical detection. The 6R-BH4 (50 mg/kg, i.p.) administration increased the accumulation of 5-HTP as an index of in vivo TRH activity under the inhibition of aromatic L-amino acid decarboxylase by NSD-1015 in the striatum of both normal control and 6-hydroxydopamine lesioned rats with intrastriatal transplants of fetal ventral mesencephalon (VM). The results suggest that TRH in the striatum of both control and VM-grafted rats is activated by 6R-BH4 penetrating into the brain from the blood.
Ishida
Y
Y
Department of Psychiatry, Miyazaki Medical College, Japan. ishiday@post.miyazaki-med.ac.jp
Todaka
K
K
Kuwahara
I
I
Hashiguchi
H
H
Ishizuka
Y
Y
Nakane
H
H
Mitsuyama
Y
Y
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016380:Brain Tissue Transplantation / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D003714:Denervation; D004622:Embryo, Mammalian; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology; D007839:Functional Laterality; D007274:Injections, Intraperitoneal; D008636:Mesencephalon / Q000502:physiology* / Q000637:transplantation; D008694:Methamphetamine / Q000494:pharmacology; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D000975:Antioxidants; D001708:Biopterins; D008694:Methamphetamine; D016627:Oxidopamine; D006916:5-Hydroxytryptophan; D014365:Tryptophan Hydroxylase; C003402:sapropterin