Long‐Term Opiate Exposure Leads to Reduction of the αi‐1 Sufyunit of GTP‐Binding Proteins

Abstract: 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 raj spinal cord‐dorsal root ganglion cocultured neurons to k‐opiate agonists is accompanied by a 60–70% reduction in the level of the αi subunit of GTP‐binding proteins. Using selective antibodies, which discriminate among the various αi subunit forms, it was found that the opiate treatment leads to a reduction in the amount of the αi‐1 subunit. The levels of αs, αo, and β subunits remain unchanged. Tnis molecular event could underlie the development of tolerance and cross‐tolerance to opiates.