Laschinski G, Kittner B, Bräutigam M
Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(2):114-8. doi: 10.1007/BF00500904.
The inhibitory effect of apomorphine on tyrosine hydroxylase (TH) was tested using enzyme preparations from rat striatum, neuroblastoma clone N1E-115 and pheochromocytoma clone PC-12. When the striatal enzyme preparation was incubated at pH 7.2 with (6R,S)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as cofactor (100-1,000 mumol/l), the IC50 for apomorphine was found to be in the 0.1-1 mumol/l range depending on the BH4-concentration used. Changing the incubation medium to pH 6.0 yielded an IC50 of about 2.5 mumol/l (BH4 = 100 mumol/l). Apomorphine was even less effective when 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine (100 mumol/l) was used as cofactor (IC50 approximately 10 mumol/l). Similar results were obtained with the enzyme preparations of the two cell clones. These experiments show that, even in low concentrations, apomorphine inhibits TH directly, provided more physiological test conditions are used. The relevance of these results for the autoreceptor-mediated mechanism of the apomorphine action on catecholamine synthesis is discussed.
使用大鼠纹状体、神经母细胞瘤克隆N1E - 115和嗜铬细胞瘤克隆PC - 12的酶制剂，测试了阿扑吗啡对酪氨酸羟化酶（TH）的抑制作用。当纹状体酶制剂在pH 7.2下与（6R，S）-L-赤藓糖-5,6,7,8-四氢生物蝶呤（BH4）作为辅因子（100 - 1000 μmol/l）一起孵育时，根据所使用的BH4浓度，阿扑吗啡的IC50在0.1 - 1 μmol/l范围内。将孵育介质改为pH 6.0时，IC50约为2.5 μmol/l（BH4 = 100 μmol/l）。当使用2-氨基-4-羟基-6,7-二甲基-5,6,7,8-四氢蝶呤（100 μmol/l）作为辅因子时，阿扑吗啡的效果更差（IC50约为10 μmol/l）。两个细胞克隆的酶制剂也得到了类似的结果。这些实验表明，即使在低浓度下，只要使用更符合生理的测试条件，阿扑吗啡就能直接抑制TH。讨论了这些结果与阿扑吗啡对儿茶酚胺合成的自受体介导机制的相关性。
