buprenorphine and Glioma

To study the mechanism underlying the difference in physical dependence potential of morphine (Mor), methadone (Met), buprenorphine (Bup), etorphine (Eto), and dihydroetorphine (DHE).. Adenylate cyclase of NG108-15 cells were used for studying the effects of different opiates on cAMP second messenger system.. 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.. There were distinct differences among these opiates in regulating cAMP second messenger system, which was related to their physical dependence potential.

Topics: Adenylyl Cyclases; Analgesics, Opioid; Buprenorphine; Cyclic AMP; Etorphine; Glioma; Humans; Hybrid Cells; Methadone; Morphine; Neuroblastoma; Opioid-Related Disorders; Receptors, Opioid; Receptors, Opioid, delta; Tumor Cells, Cultured

To study the mechanism of opioid agonists in regulation of cAMP second messenger system.. Low-pH treatment was used to deplete the stimulatory G protein (Gs) function. The effects of some opiates on adenylate cyclase were compared between control and low-pH treatment membranes.. In contrast to dehydroetorphine (DHE), etorphine (Eto), morphine (Mor) and methadone (Met) substantially increased the inhibitory effects on adenylate cyclase in membranes prepared from naive and chronic Mor- or Met-treated NG108-15 cells by low-pH treatment. In contrast to Mor, DHE and Eto did not result in significant decrease in the inhibitory effects on adenylate cyclase in membranes from the cells treated chronically with DHE or Eto. Marked rebound of adenylate cyclase was also not observed in membranes from chronic DHE or Eto-treated cells when precipitated with naloxone. Low-pH treatment eliminated naloxone-induced rebound of adenylate cyclase in chronic Mor-treated cells.. The difference in opiate-induced functional adaptive alteration of Gs is at least one biochemical mechanism of developing opiate tolerance and dependence.

Topics: Adenylyl Cyclases; Analgesics, Opioid; Buprenorphine; Cyclic AMP; Etorphine; Glioma; Humans; Hybrid Cells; Hydrogen-Ion Concentration; Methadone; Morphine; Neuroblastoma; Opioid-Related Disorders; Receptors, Opioid, delta; Tumor Cells, Cultured