Enhancement of in Vivo Dopamine Release from the Rat Striatum by 6R-L-Erythro-5,6,7,8-Tetrahydrobiopterin as Studied by Brain Dialysis
6R-L-erythro-5,6,7,8-Tetrahydrobiopterin (6R-BH4) is a natural cofactor for tyrosine hydroxylase, a rate-limiting enzyme for biosynthesis of catecholamines (Nagatsu et al., 1964). Since the concentration of 6R-BH4 in the brain (Fukushima and Nixon, 1980) is low compared with Km values of tyrosine hydroxylase (Nelson and Kaufman, 1987), tissue levels of 6R-BHA are considered to regulate the activity in vivo of this enzyme. Our previous findings that intracerebroventricular administration of 6R-BH4 resulted in enhanced tyrosine hydroxylation in the rat brain (Miwa et al., 1985) supported this possibility. In the same report, increases in the content of metabolites of dopamine, which is an index of the activity of dopaminergic neuron, was noted. Furthermore, administration of 6R-BH4 has been reported to improve clinical symptoms of Parkinson’s disease (Cutius et al., 1984). These data taken together suggest that 6R-BH4 enhances release of catecholamine from nerve terminals. Therefore, in the present study, the effects of 6R-BH4 on dopamine release in vivo was investigated using a brain dialysis method.
KeywordsTyrosine Hydroxylase Dopamine Release Ringer Solution Dopamine Level Perfusion Fluid
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- Curtius H.-C., Niederwieser A., Levine R.A., and Muldner H. (1984) Therapeutic efficacy of tetrahydrobiopterin in Parkinson’s disease, in Parkinson-specific motor and mental disorders: role of the pallidum; Pathophysiological, biochemical, and therapeutic aspects; Advances in Neurology, Vol. 40, ( Hassler R.G. and Christ J.F., eds), pp. 463–466. Raven Press, New York.Google Scholar
- Hayashi Y., Miwa S., Lee K., Koshimura K., Kamei A., Hamahata K., and Fujiwara M. (1988) A nonisotopic method for determination of the in vivo activities of tyrosine hydroxylase in the rat adrenal gland. Anal. Biochem. 168, 176–183.Google Scholar
- Levine R.A., Miller L.P., and Lovenberg W. (1981) Tetrahydrobiopterin in striatum: Localization in dopamine nerve terminals and role in catecholamine synthesis. Science 214, 919–921.Google Scholar
- Miwa S., Watanabe Y., and Hayaishi O. (1985) 6R-L-erythro-5,6,7,8-tetrahydrobiopterin as a regulator of dopamine and serotonin biosynthesis in the rat brain. Arch. Biochem. Biophys. 239, 234–241.Google Scholar
- Nagatsu T., Levitt M., and Udenfriend S. (1964) Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J. Biol. Chem. 239, 29102917.Google Scholar