Regulatory mechanism of dopamine biosynthesis in the striatum of transgenic mice carrying human tyrosine hydroxylase gene.
We investigated the regulatory mechanism of dopamine biosynthesis in the striatum of transgenic mice carrying multiple copies of human tyrosine hydroxylase (TH). The in vitro TH activity of transgenic striatum at pH 7.0 was approximately 2.8-fold higher than that of non-transgenic striatum. This augmentation is similar to that of the in vitro TH activity at pH 6.0, indicating that the expression of human TH in transgenic striatum induced little change in the phosphorylation level of TH. L-3,4-Dihydroxyphenylalanine (DOPA) formation in striatal slices of transgenic mice was approximately 2.7-fold higher than that of non-transgenic mice. The addition of 0.5 mM (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) to the incubation medium brought a negligible increase in DOPA formation in both cases. These results suggest that 6R-BH4 is not the limiting factor of TH in situ both in the transgenic and non-transgenic mice.
Kiuchi
K
K
Department of Pharmacology, Nagoya University School of Medicine, Japan.
Kiuchi
K
K
Kaneda
N
N
Sasaoka
T
T
Hidaka
H
H
Nagatsu
T
T
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics*
D001708:Biopterins; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; C003402:sapropterin; D004298:Dopamine