吗啡依赖小鼠脑组织cGMP水平、鸟苷酸环化酶及磷酸二酯酶活性的调节  

MODULATION OF cGMP LEVELS, SOLUBLE GUANYLATE CYCLASE AND PHOSPHODIESTERASE ACTIVITIES IN BRAIN OF MORPHINE DEPENDENT MICE

作　　者：方芳[1,2] 宋福津[1,2] 曹清 王艳红[1,2] 刘景生[1,2] 

机构地区：[1]中国医学科学院中国协和医科大学基础医学研究所 [2]北京协和医院病理科

出　　处：《药学学报》1998年第12期896-900,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金;博士点基金

摘　　要：以递增剂量吗啡ｓｃ，使小鼠产生对吗啡的躯体依赖，观察脑组织ｃＧＭＰ水平、ＰＤＥ和ｓＧＣ的活性变化及ＰＫＡ对其磷酸化调节。结果表明，（１）小脑、纹状体、海马及大脑皮质ｃＧＭＰ含量显著降低；（２）在小脑、海马中ｓＧＣ活性明显降低，ＰＤＥ活性无明显变化，在纹状体及大脑皮质中均明显升高，且体外磷酸化水平也均明显下降，ＰＫＡ抑制剂可抑制此变化；（３）纳洛酮拮抗组未见上述变化。结果提示，吗啡依赖小鼠脑组织ｃＧＭＰ水平普遍降低，在小脑和海马可能因ｓＧＣ活性下降引起，在纹状体及大脑皮质可能因ＰＤＥ活性升高所致。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.

关 键 词：吗啡依赖 鸟苷酸环化酶 磷酸二酯酶 CGMP 

分 类 号：R992[医药卫生—毒理学] R996[医药卫生—药学]