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UP-REGULATION OF NO-cGMP SIGNAL TRANSDUCTION SYSTEM IS INVOLVED IN THE BIOLOGICAL MECHANISMS OF OPIATE TOLERANCE AND WITHDRAWAL

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Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 8

DOI:: 10.3321/j.issn:0513-4870.2000.08.002

Key Word:: δ-阿片受体;阿片类依赖;一氧化氮合酶;环磷酸鸟苷;信号转导

Abstract：目的观察阿片激动剂长时程作用对NO-cGMP信号转导系统的影响.方法选用iNOS cDNA稳定表达的NG-LNCXiNOS细胞,采用NOS活性和cGMP放免测定,Western杂交和NADPH黄递酶组化染色技术.结果阿片类药物长时程作用剂量依赖性增高胞浆相iNOS活性和胞内cGMP含量,药物作用强弱顺序是DPDPE> DADLE>吗啡,EC50都在nmol·L-1数量级.用纳洛酮急性戒断阿片耐受细胞,造成酶活性和cGMP水平增加更显著.DPDPE长时程作用还引起iNOS基因表达增强和NADPH黄递酶染色阳性细胞增多.结论提示NO-cGMP信号转导系统上调可能是阿片耐受和成瘾的重要生化改变.

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