Long-term opiate exposure leads to reduction of the alpha i-1 subunit of GTP-binding proteins.
Desensitization or tolerance is a major consequence of long-term opiate exposure. The mechanism of opiate desensitization is only poorly understood. We report that exposure of rat spinal cord-dorsal root ganglion cocultured neurons to kappa-opiate agonist is accompanied by a 60-70% reduction in the level of the alpha i subunit of GTP-binding proteins. Using selective antibodies, which discriminate among the various alpha i subunit forms, it was found that the opiate treatment leads to a reduction in the amount of the alpha i-1 subunit. The levels of alpha s, alpha o, and beta subunits remain unchanged. This molecular event could underlie the development of tolerance and cross-tolerance to opiates.
Attali
B
B
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Vogel
Z
Z
D015153:Blotting, Western; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013997:Time Factors
D009294:Narcotics; D019204:GTP-Binding Proteins