Boadle-Biber M C, Johannessen J N, Narasimhachari N, Phan T H
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Eur J Pharmacol. 1987 Jul 9;139(2):193-204. doi: 10.1016/0014-2999(87)90252-4.
Acute morphine produced a dose-dependent, naloxone-sensitive, reversible increase in tryptophan hydroxylase activity in low speed supernatants of midbrain, pons-medulla and cerebral cortex but not spinal cord. The increase in cortical enzyme activity was blocked by 6-hydroxydopamine pretreatment, could be reversed in vitro by incubation with alkaline phosphatase and was non-additive with the increase in enzyme activity induced in the presence of phosphorylating conditions. Morphine administration produced an increase in Vmax but no change in Km of cortical enzyme for substrate, tryptophan, or the artificial reduced pterin cofactor, 6-methyl-5,6,7,8-tetrahydropterin. The failure of morphine to increase spinal tryptophan hydroxylase activity despite enhancement of enzyme activity in medulla indicates regional differences in responsiveness of the enzyme to in vivo activation.
急性吗啡可使中脑、脑桥-延髓和大脑皮质低速上清液中色氨酸羟化酶活性呈剂量依赖性、纳洛酮敏感且可逆地增加，但脊髓中未出现这种情况。皮质酶活性的增加可被6-羟基多巴胺预处理阻断，在体外与碱性磷酸酶孵育后可逆转，并且与在磷酸化条件下诱导的酶活性增加无叠加作用。给予吗啡会使皮质酶对底物色氨酸或人工还原型蝶呤辅因子6-甲基-5,6,7,8-四氢蝶呤的Vmax增加，但Km不变。尽管吗啡能增强延髓中酶的活性，却未能增加脊髓色氨酸羟化酶的活性，这表明该酶对体内激活的反应存在区域差异。
