Olgiati V R, Algeri S, Stramentinoli G
Pharmacol Res Commun. 1987 Mar;19(3):231-40. doi: 10.1016/0031-6989(87)90066-x.
The biochemical effects of 6-methyltetrahydropterin (6-MPH4), a synthetic analogue of tetrahydrobiopterin (BH4), the hydroxylase cofactor, were investigated on striatal dopaminergic neurons in the rat. Although a single parenteral dose of 6-MPH4 (18 or 54 mg/kg) did not significantly increase the content of dopamine (DA) or its acidic metabolites, L-didrohyphenylanine (L-DOPA) accumulation after decarboxylase inhibition was evident in rats receiving 54 mg/kg of 6-MPH4. On the other hand, 6-MPH4 (18 mg/kg) potentiated the reserpine-induced DA metabolism as demonstrated by increased HVA levels. In a behavioural test, 6-MPH4 partially prevented haloperidol-induced catalepsy. BH4 concentrations could thus be subsaturating with respect to tyrosine hydroxylase (TH), particularly when the enzyme activity is stimulated and the results suggest that cofactor supply may have pharmacological significance.
研究了四氢生物蝶呤（BH4）的合成类似物6-甲基四氢蝶呤（6-MPH4）对大鼠纹状体多巴胺能神经元的生化作用。四氢生物蝶呤是羟化酶的辅助因子。尽管单次腹腔注射剂量为18或54mg/kg的6-MPH4并未显著增加多巴胺（DA）及其酸性代谢产物的含量，但在接受54mg/kg 6-MPH4的大鼠中，脱羧酶抑制后L-二羟苯丙氨酸（L-DOPA）的积累是明显的。另一方面，如高香草酸（HVA）水平升高所示，6-MPH4（18mg/kg）增强了利血平诱导的DA代谢。在行为测试中，6-MPH4部分预防了氟哌啶醇诱导的僵住症。因此，相对于酪氨酸羟化酶（TH），BH4浓度可能处于亚饱和状态，特别是当酶活性受到刺激时，结果表明辅助因子的供应可能具有药理学意义。
