Kiuchi K, Kiuchi K, Kaneda N, Sasaoka T, Hidaka H, Nagatsu T
Department of Pharmacology, Nagoya University School of Medicine, Japan.
Neurosci Lett. 1993 Mar 5;151(1):55-8. doi: 10.1016/0304-3940(93)90044-l.
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.
我们研究了携带多个拷贝人类酪氨酸羟化酶（TH）的转基因小鼠纹状体中多巴胺生物合成的调控机制。转基因纹状体在pH 7.0时的体外TH活性比非转基因纹状体高约2.8倍。这种增强与pH 6.0时的体外TH活性相似，表明转基因纹状体中人类TH的表达在TH磷酸化水平上引起的变化很小。转基因小鼠纹状体切片中L-3,4-二羟基苯丙氨酸（DOPA）的生成比非转基因小鼠高约2.7倍。在孵育培养基中添加0.5 mM（6R）-L-赤藓糖型-5,6,7,8-四氢生物蝶呤（6R-BH4），在两种情况下DOPA生成的增加都可忽略不计。这些结果表明，6R-BH4在转基因和非转基因小鼠中均不是TH原位的限制因素。
