Opioid inhibition of Ih via adenylyl cyclase.
Opioids are coupled through G proteins to both ion channels and adenylyl cyclase. This study describes opioid modulation of the voltage-dependent cation channel, Ih, in cultured guinea pig nodose ganglion neurons. Forskolin, PGE2, and cAMP analogs shifted the voltage dependence of activation of Ih to more depolarized potentials and increased the inward current at -60 mV. Opioids had no effect on Ih alone, but reversed the effect of forskolin on Ih. This action of opioids was blocked by naloxone. Opioids had no effect on Ih in the presence of cAMP analogs, suggesting that modulation occurs at the level of adenylyl cyclase. The shift in the voltage dependence of Ih by agents that induce inflammation (i.e., PGE2) is one potential mechanism to mediate an increased excitability. Opioid inhibition of adenylyl cyclase and subsequent inhibition of Ih may be a mechanism by which opioids inhibit primary afferent excitability and relieve pain.
Ingram
S L
SL
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Williams
J T
JT
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D002412:Cations; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D004553:Electric Conductivity; D004723:Endorphins / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D002412:Cations; D004723:Endorphins; D004745:Enkephalins; D007473:Ion Channels; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005576:Colforsin; D004744:Enkephalin, Methionine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone