The stimulatory effects of opioids and their possible role in the development of tolerance.
Opioids have stimulatory as well as the traditional inhibitory effects on neurotransmission, but the underlying mechanisms are poorly understood. Here, Darren Smart and David Lambert review the stimulatory effects of opioids on second messengers, including inositol (1,4,5)-trisphosphate (IP3), protein kinase C (PKC), Ca2+, and cAMP, and propose that these coordinated changes at the cellular level underlie the facilitatory effects of opioids on neurotransmission. The evidence for a possible role for these stimulatory effects, particularly the activation of PKC by opioids, in the development of tolerance is also discussed.
Smart
D
D
Parke-Davis Neuroscience Research Centre, Cambridge University, UK.
Lambert
D G
DG
D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004361:Drug Tolerance; D004789:Enzyme Activation / Q000187:drug effects; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D009294:Narcotics; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium