吗啡长时程作用对小鼠脑组织蛋白激酶A及C活性的影响

Influence of Chronic Morphine Treatment on Ptotein Kinase A and Protein Kinase C Activities in the Mice Brain

本文通过复制小鼠吗啡耐受依赖模型，观察了吗啡长时程作用对小鼠脑组织ＰＫＡ及ＰＫＣ活性的影响。结果发现：（１）吗啡耐受依赖小鼠纹状体、海马、大脑皮层神经细胞胞浆ＰＫＡ活性显著升高，而小脑胞浆及以上各部位膜相ＰＫＡ活性变化不明显；（２）不同脑组织中ＰＫＣ活性变化不同，吗啡耐受依赖小鼠大脑皮层及小脑胞浆ＰＫＣ活性明显升高，在纹状体胞浆则显著下降，但纹状体膜相ＰＫＣ活性却显著增加，海马及小脑膜相ＰＫＣ活性则明显降低；（３）纳洛酮可拮抗吗啡引起的上述变化。结果提示：一些脑组织胞浆ＰＫＡ活性的升高、ＰＫＣ活性的变化以及可能存在的ＰＫＣ于胞浆和膜相之间的移位可能是吗啡耐受依赖的重要生化基础，且此变化可能由阿片受体所介导。

The aim of this study was to determine whether chronic morphine treatment could influence the protein kinase A and protein kinase C activities in the mice brain. The results showed that : ( 1 ) chronic morphine administration apparently enhanced cytosolic - PKA activity in striatum , hippocampus , cerebral cortex ; ( 2 ) the changes of PKC activity were various in the different brain regions. Chronic morphine treatment sigificantly increased cytosolic PKC activity in cerebellum and cerebral cortex , but decneased in striatum. Chronic morphine administration also increased membrane PKC activity in striatum , but decreased in hippocampus and cerebellum;( 3 ) Concomitant administration of the opioid receptor antagonist naloxone was found to block the effects of chronic morphine treatment on protein kinase activity. It seems that the changes of PKA and PKC activities , the possible translocation of PKC between the cytosol and membrane might be responsible for the mechanism of opiate tolerance and ependence.