Uncoupling of receptors is essential for opiate-induced desensitization (tolerance) in neuroblastoma x glioma hybrid cells NG 108-15.
Neuroblastoma x glioma hybrid cells NG 108-15 were chronically treated with opioid agonists and tested for their development of "tolerance" as evaluated by the loss of inhibitory activity of opioids upon cAMP-accumulation. Desensitization was dose-dependent and non-competitive and highly selective, since the activity of other, non-opioid inhibitory compounds, such as noradrenaline and carbachol, was not altered. Moreover, naloxone-induced "withdrawal signs" (revealed in the lack of change in cAMP) were lacking in preparations completely desensitized ("tolerant") towards opiate effects. These results reject the assumption of a common biochemical mechanism underlying both opiate tolerance and dependence and rather support the significance of an uncoupling of receptors from subsequent effector systems upon chronic opiate action.
D000818:Animals; D002460:Cell Line; D004745:Enkephalins / Q000494:pharmacology*; D005910:Glioma / Q000503:physiopathology*; D006822:Hybrid Cells / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D051379:Mice; D009294:Narcotics / Q000494:pharmacology*; D009447:Neuroblastoma / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology*
D004745:Enkephalins; D009294:Narcotics; D011957:Receptors, Opioid; D009638:Norepinephrine