Nongenomic mechanisms of glucocorticoid inhibition of nicotine-induced calcium influx in PC12 cells: Involvement of protein kinase C

Nongenomic mechanisms of corticosterone (B) inhibition of nicotine (Nic)-induced calcium influx were investigated in PC12 cells. Corticosterone could rapidly inhibit the Ca²⁺ influx induced by Nic, and BSA-conjugated B had a similar inhibitory effect. The inhibition of Nic-induced Ca²⁺ influx by B could be mimicked by protein kinase C (PKC) activator (phorbol 12- myristate 13-acetate) and reversed by PKC inhibitors, chelerythrine chloride and Go6976. When PC 12 cells were pretreated with pertussis toxin, the inhibitory effect of B on Nic-induced Ca²⁺ influx was blocked. Both B and BSA-conjugated B could activate PKC activity, with the maximal responses at 10^-9 and 10^-7 M at 37 C, respectively. The dose-response curve was bell shaped. At 25 C, however, the dose-response curve considerably shifted to the right, and B was most potent at 10^-5 M. The time course showed that PKC activity was highest at 5 min of B's action. The results suggest that B might act via putative membrane receptors and inhibit the Ca²⁺ influx induced by Nic through the pertussis toxin-sensitive G protein-PKC pathway and that PKC plays an important role in the mechanisms of glucocorticoid nongenomic action.