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EVIDENCE FOR INVOLVEMENT OF NO/NOS-cGMP SIGNAL SYSTEM IN MORPHINE DEPENDENC
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- Author:
- No author available
- Journal Title:
- ACTA PHTYSIOLOGOCA SINICA
- Issue:
- 2
- DOI:
- 10.3321/j.issn:0371-0874.1999.02.003
- Key Word:
- 吗啡;依赖;一氧化氮合酶(NOS);cGMP;磷酸化
Abstract： 本文观察了吗啡依赖小鼠脑组织cGMP含量、钙依赖性及非钙依赖性NOS活性的变化、蛋白激酶A(protein kinase A, PKA)对NOS活性的磷酸化调节以及一氧化氮合酶(NOS)抑制剂对吗啡依赖形成的影响.结果发现: (1)小脑、纹状体、海马及大脑皮质cGMP含量明显下降;(2)纹状体及大脑皮质钙依赖性NOS活性明显升高, 而IP20(PKA抑制剂)可抑制此变化, 小脑及海马钙依赖性NOS活性及以上各脑区非钙依赖性NOS活性无明显变化;(3)纹状体、大脑皮质中与NOS分子量相当的150 kD蛋白质的体外磷酸化水平低于对照, IP20 可抑制此变化;(4) NOS抑制剂可抑制小鼠对吗啡依赖的形成;(5)纳洛酮拮抗组小鼠未见上述变化.结果表明, 吗啡依赖小鼠脑组织普遍存在cGMP水平下降, 纹状体、大脑皮质钙依赖性NOS活性的增加可能与吗啡依赖有关, 且受PKA对其磷酸化调节.NOS活性增加与cGMP含量的下降相矛盾, 提示NO/NOS在吗啡依赖中的作用可能是通过一种不同于产生cGMP信号的机制进行的.
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