The protein kinase C activator 1-oleoyl-2-acetylglycerol inhibits voltage-dependent Ca2+ current in the pituitary cell line AtT-20.
The role of protein kinase C in regulating Ca2+ channel activity was investigated using the whole-cell patch-clamp technique in the mouse pituitary tumor cell line AtT-20. The Ca2+ current was activated by depolarizing voltage steps from a holding potential of -80 mV. Extracellular application of the protein kinase C activator 1-oleoyl-2-acetylglycerol (OAG) reduced voltage-dependent Ca2+ current. This effect was reversible and dose dependent (10-100 microM). Pertussis toxin did not block the effect of OAG on Ca2+ current, suggesting that OAG does not affect Ca2+ channels via a pertussis toxin sensitive guanosine triphosphate binding protein. Na+-free solutions did not block the effect of OAG on Ca2+ channels, suggesting that this effect of OAG does not involve the Na+/H+ antiporter. The phorbol esters 12-deoxyphorbol-13-isobutyrate (10 microM) and phorbol-12,13-diacetate (100 microM) also reduced Ca2+ current. The results suggest that protein kinase C may be an inhibitory regulator of voltage-dependent Ca2+ channels.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology*; D004558:Electric Stimulation; D005989:Glycerides / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D037342:Pertussis Toxin; D010703:Phorbol Esters / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004075:Diglycerides; D005989:Glycerides; D007473:Ion Channels; D010703:Phorbol Esters; D010566:Virulence Factors, Bordetella; C039067:12-deoxyphorbol 13-isobutyrate; C038237:1-oleoyl-2-acetylglycerol; D012964:Sodium; D037342:Pertussis Toxin; D011493:Protein Kinase C; D002118:Calcium