DIRECT INHIBITION OF TYROSINE-HYDROXYLASE FROM PC-12 CELLS BY CATECHOL DERIVATIVES
DIRECT INHIBITION OF TYROSINE-HYDROXYLASE FROM PC-12 CELLS BY CATECHOL DERIVATIVES
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DOI：
10.1007/bf00500085
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发表时间：
1986-04-01
影响因子：
3.6
通讯作者：
BRAUTIGAM, M
中科院分区：
文献类型：
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作者：
LASCHINSKI, G;KITTNER, B;BRAUTIGAM, M
研究了几种含有儿茶酚部分的药物对PC-12细胞酪氨酸羟化酶（TH）的体外抑制作用。对比所测天然化合物，多巴胺、去甲肾上腺素和2（3,4-二羟基苯基）乙醇（DOPET）最有效（IC50在1.4 ~ 3.6 .mu之间）。M为0.5 .mu。m6 (R，S)- l -红细胞-5,6,7,8-四氢生物terin作为辅助因子)。DOPA (IC50: 35 .mu。M)和3,4-二羟基苯乙酸(DOPAC; IC50: 180 .mu。M是较弱的抑制剂。在含有儿茶酚部分的合成药物中，异丙肾上腺素、（.+-。）-2-氨基-6,7-二羟基-1,2,3,4-四氢萘（6,7- adtn）和（.+-。）-2-二甲氨基-6,7-二羟基-四氢萘（TL-99）与天然儿茶酚胺具有相同的抑制作用（IC50在1.6 ~ 3.9 μ之间）。M)，而阿波啡衍生物和2,3,4,5-四氢-1-苯基-1 h -3-苯并氮平和7,8-二醇（SKF 38393）更有效（IC50: 0.5-0.8 μ M）。这些结果表明，天然儿茶酚和某些药物（例如6,7- adtn, TL-99 SKF 38393）比通常认为的更有效的酪氨酸羟化酶直接阻滞剂。在多巴胺和去甲肾上腺素的情况下，这些发现建议重新评估它们在体内酪氨酸羟化酶反馈控制中的作用。
Several drugs with a catechol moiety were studied for their potency to inhibit tyrosine hydroxylase (TH) from PC-12 cells in vitro. When the natural compounds tested were compared, dopamine, norepinephrine and 2(3,4-dihydroxyphenyl)-ethanol (DOPET) were most effective (IC50 between 1.4 and 3.6 .mu.m with 0.5 .mu.M 6(R,S)-L-erythro-5,6,7,8-tetrahydrobiopterin as cofactor). DOPA (IC50: 35 .mu.M) and 3,4-dihydroxyphenylacetic acid (DOPAC; IC50: 180 .mu.M were less potent inhibitors. Among the synthetic drugs possessing catechol moiety, isoproterenol, (.+-.)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) and (.+-.)-2-dimethylamino-6,7-dihydroxy-tetrahydronaphthalene (TL-99) had the same inhibitory effects as the natural catecholamines (IC50 between 1.6 and 3.9 .mu.M), whereas the apomorphine derivatives and 2,3,4,5-tetrahydro-1-phenyl-1 H-3-benzazepine and 7,8-diol (SKF 38393) were even more potent (IC50: 0.5-0.8 .mu.M). These results demonstrate that natural catechols and certain drugs (e.g. 6,7-ADTN, TL-99 SKF 38393) are more effective direct blockers of tyrosine hydroxylase than generally assumed provided appropriate assay conditions are used. In the case of dopamine and norepinephrine, these findings suggest a reevaluation of their role for feedback control of tyrosine hydroxylase in vivo.