Nongenomic mechanism of glucocorticoid inhibition of bradykinin-induced calcium influx in PC12 cells: possible involvement of protein kinase C

Many stimulants, including bradykinin (BK), can induce increase in [Ca2+](i) in PC 12 cells. Bradykinin induces an increase in [Ca2+](i) via intracellular Ca2+ release and extracellular Ca2+ influx through the transduction of G protein, but not through voltage-sensitive calcium channels. In this experiment, We analyzed how corticosterone (Cort) influences BK-induced intracellular Ca2+ release at id extracellular Cat + influx; and further studied the mechanism of glucocorticoid's action: To dissociate the intracellular Cat + release and extracellular Ca2+ influx induced by BK, the Ca2+-free/Ca2+-reintroduction protocol was used. The results were as follows: (1) The Ca2+ influx induced by BK could be rapidly inhibited by Cort, but intracellular Ca2+ release could not be affected significantly. (2) The inhibitory effect of Cort-BSA (BSA -conjugated Cort) on Ca2+ influx induced by BK was the same as the effect of free Cort. (3) Protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) could mimic and PKC inhibitor 666976 could reverse the inhibitory effect of Cort. (4) There was no inhibitory effect of Cort on Ca2+ influx induced by BK when pretreated with pertussis toxin. The results suggested, for the first time,that Cort might act via a putative membrane receptor and inhibit the Ca2+ influx induced by BK through the pertussis toxin sensitive G protein-PKC pathway.. (C) 2003 Elsevier Science Inc. All rights reserved.