Tetrahydrobiopterin biosynthesis in the rat brain: Heterogeneity of GTP cyclohydrolase I mRNA expression in monoamine-containing neurons
Tetrahydrobiopterin biosynthesis in the rat brain: Heterogeneity of GTP cyclohydrolase I mRNA expression in monoamine-containing neurons
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DOI：
10.1016/0197-0186(95)00124-7
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发表时间：
1996-05-01
影响因子：
4.2
通讯作者：
Kapatos, G
中科院分区：
文献类型：
--
作者：
Lentz, SI;Kapatos, G
GTP环水解酶I是生物合成四氢生物蝶呤的第一酶和限速酶。采用定量原位杂交技术在细胞水平上研究了GTP环水解酶I mRNA在大鼠脑中的表达。间脑和髓脑之间的冠状面暴露于s -35标记的反义GTP环水解酶I cRNA探针。与这些片段序列杂交的是与酪氨酸羟化酶mRNA互补的s -35标记的反义rna探针。酪氨酸羟化酶和GTP环水解酶I mrna被发现在整个大脑的儿茶酚胺神经元内共定位。在神经元中表达GTP环水解酶I mRNA的总体分布与已知的多巴胺、去甲肾上腺素/肾上腺素和含5 -羟色胺的细胞组的分布完全一致。总的来说，GTP环水解酶I mRNA的表达范围是已知的30倍，血清素中的转录物明显比多巴胺或去甲肾上腺素/肾上腺素中的转录物丰富。各5 -羟色胺细胞组间比较表明，中缝正中核、中缝尾线状核（B8）和中缝背核（B6/B7）神经元GTP环水解酶I mRNA表达水平最高。跨多巴胺细胞组的比较表明，该转录本在腹侧被盖区（A10）的神经元中比在黑质致密部（A9）的神经元中更丰富，并且A9和A10多巴胺神经元的表达水平都高于下丘脑（A11-A14）的DA神经元。蓝斑座（A6）和蓝斑下（A6v）的去甲肾上腺素神经元GTP环水解酶I mRNA水平明显高于其他去甲肾上腺素（Al和A2）或肾上腺素（C1和C2）细胞组。在已知含有一氧化氮合酶的神经元中不能明确检测到GTP环水解酶I mRNA。含单胺神经元GTP环水解酶I mRNA表达水平的异质性可能在决定四氢生物蝶呤稳态水平并最终调节单胺生物合成中起重要作用。版权所有爱思唯尔科学有限公司
GTP cyclohydrolase I is the first and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. A quantitative in situ hybridization technique was used to study the expression of GTP cyclohydrolase I mRNA in the rat brain at the cellular level. Coronal sections between the diencephalon and myelencephalon were exposed to a S-35-labelled antisense GTP cyclohydrolase I cRNA probe. Sections serial to these were hybridized with a S-35-labelled antisense cRNA probe complementary to tyrosine hydroxylase mRNA. Tyrosine hydroxylase and GTP cyclohydrolase I mRNAs were found to colocalize within catecholamine neurons located throughout the brain. The overall distribution of neurons expressing GTP cyclohydrolase I mRNA was observed to correspond exactly to the known distribution of the dopamine, norepinephrine/epinephrine and serotonin-containing cell groups, Overall, a 30-fold range of GTP cyclohydrolase I mRNA expression was observed, with the transcript being significantly more abundant in serotonin than in dopamine or norepinephrine/epinephrine neurons. Comparisons across serotonin cell groups indicated that neurons of the median raphe nucleus, caudal linear nucleus raphe (B8) and the dorsal raphe (B6/B7) expressed the highest levels of GTP cyclohydrolase I mRNA. Comparisons across dopamine cell groups indicated that the transcript was more abundant in neurons of the ventral tegmental area (A10) than in neurons of the substantia nigra pars compacta (A9)) and that both A9 and A10 dopamine neurons exhibited higher levels of expression than the DA neurons of the hypothalamus (A11-A14). Norepinephrine neurons of the locus coeruleus (A6) and subcoeruleus (A6v) exhibited significantly higher levels of GTP cyclohydrolase I mRNA than did neurons in other norepinephrine (Al and A2) or epinephrine (C1 and C2) cell groups. GTP cyclohydrolase I mRNA could not be detected unequivocally in neurons known to contain nitric oxide synthase. Heterogeneity in the level of expression of GTP cyclohydrolase I mRNA by monoamine-containing neurons may play an important role in determining steady state levels of tetrahydrobiopterin and, ultimately, the regulation of monoamine biosynthesis. Copyright (C) 1996 Elsevier Science Ltd.