El Mestikawy S, Goetz C, Pasquier A, Glowinski J, Hamon M
Brain Res. 1982 Jul 29;244(2):319-29. doi: 10.1016/0006-8993(82)90091-9.
The administration of kainic acid (1--2 micrograms) into the right striatum of adult rats resulted in a marked local increase in tryptophan hydroxylase activity (+ 54--106%). This change was significant as soon as on the second day after the treatment and persisted for at least 12 days. In addition, long-lasting elevations of tryptophan hydroxylase activity were also observed in the anterior raphe area, septum and ipsilateral hippocampus and cerebral cortex. In contrast, the intrahippocampal injection of kainic acid (1 microgram) induced a long-term increase in tryptophan hydroxylase activity only in the injected structure. In all cases, the changes in tryptophan hydroxylase activity were associated with significant increases in the Vmax of the enzyme with no alteration of its apparent affinities for tryptophan and the pterin cofactor. Studies of the sensitivity of tryptophan hydroxylase from control and from kainic acid-treated rats to in vitro activating conditions (Ca2+-dependent phosphorylation, partial trypsinization, exposure to sodium dodecyl sulfate) suggest that the intrastriatal injection of the neurotoxin induced a long-lasting activation of the enzyme. These findings indicate that intracerebral injections of kainic acid may be a valuable approach to explore further the mechanisms controlling tryptophan hydroxylase activity in vivo.
向成年大鼠右侧纹状体注射海人酸（1 - 2微克）会导致色氨酸羟化酶活性在局部显著增加（增加54% - 106%）。这种变化在治疗后第二天就很明显，并持续至少12天。此外，在前缝际区、隔区、同侧海马体和大脑皮层也观察到色氨酸羟化酶活性的长期升高。相比之下，海马体内注射海人酸（1微克）仅在注射部位诱导色氨酸羟化酶活性长期增加。在所有情况下，色氨酸羟化酶活性的变化都与该酶的Vmax显著增加相关，而其对色氨酸和蝶呤辅因子的表观亲和力没有改变。对对照大鼠和经海人酸处理的大鼠的色氨酸羟化酶对体外激活条件（钙依赖性磷酸化、部分胰蛋白酶消化、暴露于十二烷基硫酸钠）的敏感性研究表明，纹状体内注射神经毒素可诱导该酶的长期激活。这些发现表明，脑内注射海人酸可能是进一步探索体内控制色氨酸羟化酶活性机制的一种有价值的方法。
