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.