Weekley L B, Phan T, Narasimhachari N, Johannessen J, Boadle-Biber M C
Biochem Pharmacol. 1985 May 1;34(9):1549-57. doi: 10.1016/0006-2952(85)90698-7.
In vivo administration of clonidine hydrochloride (Catapres) via tail vein injection produced a rapid increase in brainstem tryptophan hydroxylase activity assayed in vitro under subsaturating conditions of reduced pterin cofactor, 6MPH4. Enzyme activity returned to and remained at control levels about 60 min after treatment with low doses of clonidine (5 micrograms/kg). However, with higher doses of the drug (15 micrograms/kg), enzyme activity fell to below control levels for about an hour. Incubation of brainstem slices with clonidine also produced a dose-dependent increase in enzyme activity. The increase in enzyme activity appears to be mediated indirectly since it was abolished when brain catecholamine levels were depleted by pretreatment with 6-hydroxydopamine 8 days prior to clonidine treatment. The kinetic properties of tryptophan hydroxylase prepared 25 and 90 min after clonidine administration indicate that the initial increase and subsequent decrease in enzyme activity seen under these conditions may be due to changes in apparent Vmax of the enzyme.
通过尾静脉注射在体内给予盐酸可乐定（凯他乐），在体外测定时，在还原蝶呤辅因子6MPH4未饱和的条件下，脑干色氨酸羟化酶活性迅速增加。用低剂量可乐定（5微克/千克）治疗后约60分钟，酶活性恢复并维持在对照水平。然而，使用较高剂量的药物（15微克/千克）时，酶活性在约一小时内降至对照水平以下。用可乐定孵育脑干切片也会使酶活性呈剂量依赖性增加。酶活性的增加似乎是间接介导的，因为在可乐定治疗前8天用6-羟基多巴胺预处理使脑儿茶酚胺水平耗尽时，这种增加就被消除了。在给予可乐定后25分钟和90分钟制备的色氨酸羟化酶的动力学特性表明，在这些条件下观察到的酶活性最初增加和随后降低可能是由于酶的表观Vmax发生了变化。
