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Enhancement of Dopamine Release In Vivo from the Rat Striatum by Dialytic Perfusion of 6 R ‐ l ‐ erythro ‐5,6,7,8‐Tetrahydrobiopterin
Author(s) -
Koshimura Kunio,
Miwa Soichi,
Lee Ken,
Fujiwara Motohatsu,
Watanabe Yasuyoshi
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb01974.x
Subject(s) - dopamine , microdialysis , tetrahydrobiopterin , striatum , chemistry , tyrosine hydroxylase , biopterin , neurochemical , catecholamine , endocrinology , medicine , in vivo , nomifensine , neurotransmitter , tyrosine , homovanillic acid , pharmacology , dopaminergic , biochemistry , serotonin , biology , enzyme , cofactor , receptor , microbiology and biotechnology
We have previously reported that intracerebroventricular administration of 6 R ‐L‐ erythro ‐5,6,7,8‐tetrahydrobiopterin (6 R ‐BH 4 ), a cofactor for tyrosine hydroxylase, enhances biosynthesis of 3,4‐dihydroxyphenylethylamine (dopamine) in the rat brain. In the present study, we have more precisely examined the effects of 6 R ‐BH 4 on dopamine release in vivo from the rat striatum using brain microdialysis. The amount of dopamine collected in striatal dialysates was determined using HPLC with electrochemical detection after purification with an alumina batch method. When the striatum was dialyzed with Ringer solution containing various concentrations of 6 R ‐BH 4 (0.25,0.5, and 1.0 m M ), dopamine levels in striatal dialysates increased in a concentration‐dependent manner. Biopterin had little effect on dopamine levels in dialysates. The 6 R ‐BH 4 ‐induced increase in dopamine levels in dialysates was abolished after pretreatment with tetrodotoxin (50 μ M ) added to the perfusion fluid, but after pretreatment with nomifensine (100 mg/kg, intraperitoneal injection), an inhibitor of dopamine uptake mechanism, a larger increase was observed. After inhibition of tyrosine hydroxylase by pretreatment with α‐methyl‐ p ‐tyrosine (250 mg/kg, intraperitoneal injection), most of the increase persisted. These results suggest that 6 R ‐BH 4 has a dopamine‐releasing action, which is not dependent on biosynthesis of dopamine.