Effects of opioid receptor agonists on cAMP second messenger system.

Abstract

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.