Choe E S, McGinty J F
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, NC 27858, USA.
Neuroscience. 2000;101(3):607-17. doi: 10.1016/s0306-4522(00)00379-1.
In vivo cyclic adenosine monophosphate (cAMP)-induced N-methyl-D-aspartate receptor and mitogen-activated protein kinase activation was investigated in the dorsal striatum by semiquantitative immunocytochemistry. Intracerebroventricular infusion of 8-bromo-adenosine 3',5'-cyclic monophosphorothioate, Sp isomer (Sp-8-Br-cAMPS), increased phosphorylated cAMP-responsive element binding protein, phosphorylated Elk-1 and Fos immunoreactivity in a dose-dependent manner. Intracerebroventricular infusion of the N-methyl-D-aspartate antagonist, MK801, decreased, but tetrodotoxin or the mitogen-activated extracellular-regulated kinase inhibitor, PD98059, did not affect Sp-8-Br-cAMPS-induced phosphorylated c-AMP-responsive element binding protein, phosphorylated Elk-1, phosphorylated extracellular-signal-regulated kinase and Fos immunoreactivity. The p38 mitogen-activated protein kinase inhibitor, SB203580, decreased the Sp-8-Br-cAMPS-induced increase in all markers, except phosphorylated extracellular-signal-regulated kinase, in a dose-dependent manner. We suggest that N-methyl-D-aspartate receptors couple c-AMP to phosphorylation events and immediate early gene induction in the nucleus of striatal medium spiny neurons. These events are mediated by crosstalk between protein kinase A and mitogen-activated protein kinase cascades in vivo.
通过半定量免疫细胞化学方法，在体内研究了环磷酸腺苷（cAMP）诱导的N-甲基-D-天冬氨酸受体和丝裂原活化蛋白激酶在背侧纹状体中的激活情况。脑室内注入8-溴-3',5'-环磷硫酰腺苷，Sp异构体（Sp-8-Br-cAMPS），以剂量依赖的方式增加了磷酸化的cAMP反应元件结合蛋白、磷酸化的Elk-1和Fos免疫反应性。脑室内注入N-甲基-D-天冬氨酸拮抗剂MK801可降低上述反应，但河豚毒素或丝裂原活化的细胞外调节激酶抑制剂PD98059不影响Sp-8-Br-cAMPS诱导的磷酸化c-AMP反应元件结合蛋白、磷酸化的Elk-1、磷酸化的细胞外信号调节激酶和Fos免疫反应性。p38丝裂原活化蛋白激酶抑制剂SB203580以剂量依赖的方式降低了Sp-8-Br-cAMPS诱导的除磷酸化细胞外信号调节激酶外的所有标志物的增加。我们认为，N-甲基-D-天冬氨酸受体将c-AMP与纹状体中等棘状神经元细胞核中的磷酸化事件和即刻早期基因诱导偶联起来。这些事件在体内由蛋白激酶A和丝裂原活化蛋白激酶级联之间的串扰介导。
