Effects of low-pH treatment on cAMP second messenger system regulated by different opioid agonists

AIM: To study the mechanism of opioid agonists in regulation of cAMP second messenger system. METHODS: Low-pH treatment was used to deplete the stimul atory G portein (G(s)) function. The effects of some opiates on adenylate c yclase were compared between control and low-pH treatment membranes. RESULT S: In contrast to dihydroetorphine (DHE), etorphine (Eto), morphine (Mor) a nd methadone (Met) substantially increased the inhibitory effects on adenyl ate cyclase in membranes prepared from naive and chronic Mor- or Met-treate d NG108-15 cells by low-pH treatment. In contrast to Mor, DHE and Eto did n ot result in significant decrease in the inhibitory effects on adenylate cy clase in membranes from the cells treated chronically with DHE or Eto. Mark ed rebound of adenylate cyclase was also not observed in membranes from chr onic DHE or Eto-treated cells when precipitated with naloxone. Low-pH treat ment eliminated naloxone-induced rebound of adenylate cyclase in chronic Mo r-treated cells. CONCLUSION: The difference in opiate-induced functional ad aptive alteration of G(s) is at least one biochemical mechanism of developi ng opiate tolerance and dependence.