Fang F, Song F, Cao Q, Wang Y, Liu J
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005.
Yao Xue Xue Bao. 1998 Dec;33(12):896-900.
By inducing morphine dependence in mice, the changes of cGMP contents, phosphodiesterase (PDE) and soluble guanylate cyclase (sGC) activities and their phosphorylation regulated by protein kinase A (PKA) were observed. It was found that: (1) cGMP contents in cerebellum, striatum, hippocampus and cerebral cortex were significantly lower. (2) The sGC activities were apparently decreased in cerebellum and striatum. In the striatum and cerebral cortex the sGC activities and phosphorylation levels in vitro were significantly increased and were inhibited by PKA inhibitor. (3) The PDE activities showed no change in cerebellum and hippocampus, but in striatum and cerebral cortex PDE activities and phosphorylation levels in vitro were significantly increased and were inhibited by PKA inhibitor. (4) These changes described above were not observed in mice treated with naloxone 30 min prior to daily morphine injection. Our data indicate that the decrease of cGMP contents occurred generally in brain regions of morphine-dependent mice. The decrease of cGMP contents in cerebellum and hippocampus may be due to the decrease of sGC activities, but the decrease of cGMP contents in striatum and cerebral cortex may be mainly due to the increase of PDE activity. Both sGC and PDE activities were regulated by PKA.
通过诱导小鼠吗啡依赖，观察环磷酸鸟苷（cGMP）含量、磷酸二酯酶（PDE）和可溶性鸟苷酸环化酶（sGC）活性的变化以及它们受蛋白激酶A（PKA）调节的磷酸化情况。结果发现：（1）小脑、纹状体、海马和大脑皮层中的cGMP含量显著降低。（2）小脑和纹状体中的sGC活性明显降低。在纹状体和大脑皮层中，体外sGC活性和磷酸化水平显著升高，并被PKA抑制剂抑制。（3）小脑和海马中的PDE活性无变化，但纹状体和大脑皮层中的PDE活性和体外磷酸化水平显著升高，并被PKA抑制剂抑制。（4）在每日注射吗啡前30分钟用纳洛酮处理的小鼠中未观察到上述变化。我们的数据表明，吗啡依赖小鼠的脑区普遍出现cGMP含量降低。小脑和海马中cGMP含量的降低可能是由于sGC活性降低，但纹状体和大脑皮层中cGMP含量的降低可能主要是由于PDE活性增加。sGC和PDE活性均受PKA调节。
