Kinase C activator 1,2-oleoylacetylglycerol attenuates voltage-dependent calcium current in sensory neurons.
The diacylglycerol analogue 1,2-oleoylacetylglycerol (OAG) and the phorbol ester 12-deoxyphorbol 13-isobutyrate (DPB) were tested for their effects on the voltage-dependent calcium (Ca) current in embryonic chicken dorsal root ganglion neurons in vitro. OAG (0.6-60 microM) and DPB (0.01-50 microM) produced reversible decreases in Ca current. Neither drug affected resting membrane conductance, the voltage-dependent potassium current, or the Ca current-voltage relationship. The concentrations of OAG and DPB that reduced Ca current correlate well with those concentrations that have been shown, in other systems, to activate protein kinase C-dependent phosphorylation. The time course for OAG action on Ca current is also consistent with an involvement of kinase C. Incubation of dorsal root ganglion cells in 60 microM OAG prevented further reductions in Ca current by either 50 microM DPB or 10 microM norepinephrine, a known modulator of the voltage-dependent Ca channel in these cells. This evidence suggests that protein kinase C may play a role in modulating Ca channel function.
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002642:Chick Embryo; D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology; D005989:Glycerides / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D009475:Neurons, Afferent / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*
D004075:Diglycerides; D005989:Glycerides; D007473:Ion Channels; D010703:Phorbol Esters; C039067:12-deoxyphorbol 13-isobutyrate; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine