I 型代谢型谷氨酸受体通过依赖 CaMKII 的途径控制大鼠纹状体中 CREB、Elk-1 和 ERK 的磷酸化。

Group I metabotropic glutamate receptors control phosphorylation of CREB, Elk-1 and ERK via a CaMKII-dependent pathway in rat striatum.

作者信息

Choe E S, Wang J Q

机构信息

Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes Street, M3-C15, Kansas City, MO 64108, USA.

出版信息

Neurosci Lett. 2001 Nov 9;313(3):129-32. doi: 10.1016/s0304-3940(01)02258-3.

DOI:10.1016/s0304-3940(01)02258-3

PMID:11682144

Abstract

In vivo activation of group I metabotropic glutamate receptors (mGluRs) upregulates phosphorylation of cyclic AMP response element-binding protein (CREB), Elk-1 and extracellular signal-regulated kinases (ERK) in striatal neurons. To evaluate putative roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in CREB, Elk-1 and ERK phosphorylation, the CaMKII inhibitor, KN62, was infused simultaneously with the group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG), into the rat dorsal striatum. The results showed that DHPG (125, 250, and 500 nmol) increased phosphorylated (p) CaMKII immunoreactivity (IR) in a dose-dependent manner. KN62 (50 nmol) significantly attenuated 500 nmol DHPG-induced pERK, pElk-1 and pCREB IR in the ipsilateral dorsal striatum. These data indicate that pCaMKII is a possible upstream effector that is responsible for the regulation of CREB, Elk-1 and ERK phosphoproteins in response to group I mGluR stimulation in striatal neurons.

摘要

I 型代谢型谷氨酸受体（mGluRs）在体内的激活会上调纹状体神经元中环磷酸腺苷反应元件结合蛋白（CREB）、Elk-1 和细胞外信号调节激酶（ERK）的磷酸化水平。为了评估钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）在 CREB、Elk-1 和 ERK 磷酸化过程中的假定作用，将 CaMKII 抑制剂 KN62 与 I 型 mGluR 激动剂 3,5-二羟基苯甘氨酸（DHPG）同时注入大鼠背侧纹状体。结果显示，DHPG（125、250 和 500 nmol）以剂量依赖性方式增加磷酸化（p）CaMKII 的免疫反应性（IR）。KN62（50 nmol）显著减弱了 500 nmol DHPG 诱导的同侧背侧纹状体中 pERK、pElk-1 和 pCREB 的 IR。这些数据表明，pCaMKII 可能是一种上游效应器，负责在纹状体神经元中响应 I 型 mGluR 刺激时对 CREB、Elk-1 和 ERK 磷酸蛋白的调节。