不同的阿片受体激动剂对环腺苷—磷酸第二信使系统的作用(英文)

Effects of opioid receptor agonists on cAMP second messenger system

目的:研究吗啡(Mor)、美沙酮(Met)、丁丙诺啡(Bup)、二氢埃托啡(DHE)和埃托啡(Eto)躯体依赖性差别的机制,方法:用NG108-15细胞模型,观察不同的阿片受体激动剂对cAMP第二信使系统的作用,结果:细胞分别暴露于Mor,Met,Bup各10 μmol·L^(-1)和DHE,Eto各10 nmol·L^(-1),24 h或72 h后,用纳洛酮10 μmol·L_(-1)催促,Mor组cAMP水平明显反跳性升高,其他各组cAMP反跳水平虽有一定程度的升高,但幅度较Mor组低得多.用Met,Bup,DHE和Eto替代处理Mor预处理48 h的NG108-15细胞,可使Nal催促的cAMP反跳水平明显降低,结论:Mor,Met,Bup,DHE和Eto对cAMP第二信使系统的作用明显不同,这与它们的躯体依赖性有关。

AIM: To study the mechanism underlying the difference in physical dependence potential of morphine (Mor), methadone ( Met), buprenorphine (Bup), etorphine ( Eto ), and dihydroetorphine ( DHE ). METHODS: Adenylate cyclase of NG108-15 cells were used for studying the effects of different opiates on cAMP second messenger system. RESULTS: Bup, DHE, and Eto were distinct from Mor in naloxone-precipitated rebound response of cAMP in NG108-15 cells chronically treated with these opiates. Naloxone given to NG108-15 cells treated with Mor for 24 h produced marked rebound response of adenylate cyclase. While no such rebound response was detected when the cells were treated with Bup, DHE, and Eto for 24 h. The naloxone-induced rebound response of cAMP in chronic Met-treated NG108-15 cells was also lower than that in chronic Mor-treated NG108-15 cells. Following a prolonged exposure to Bup, DHE, and Eto for 72 h, the naloxone-induced rebound response of cAMP in these cells was still markedly lower than that in Mor-treated cells. The substitution of Mor with Bup, Met, DHE, and Eto inhibited naloxone-induced rebound response of cAMP in chronic Mor-treated NG108-15 cells. CONCLUSION: There were distinct differences among these opiates in regulating cAMP second messenger system, which was related to their physical dependence potential.