Effects of opioid receptor agonists on cAMP second messenger system

AIM: To study the mechanism underlying the difference in physical dependenc e potential of morphine (Mor), methadone (Met), buprenorphine (Bup), etorph ine (Eto), and dihydroetorphine (DHE). METHODS: Adenylate cyclase of NG108- 15 cells were used for studying the effects of different opiates on cAMP se cond messenger system. RESULTS: Pup, DHE, and Eto were distinct from Mor in naloxone-precipitated rebound response of cAMP in NG108-15 cells chronical ly treated with these opiates. Naloxone given to NG108-15 cells treated wit h 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 c hronic Met-treated NG108-15 cells was also lower than that in chronic Mor-t reated 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 Mo r with Bup, Met, DHE, and Eto inhibited naloxone-induced rebound response o f cAMP in chronic Mor-treated NG108-15 cells. CONCLUSION: There were distin ct differences among these opiates in regulating cAMP second messenger syst em, which was related to their physical dependence potential.