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

Life Sci. 2003 Apr 18;72(22):2533-42. doi: 10.1016/s0024-3205(03)00168-1.


Many stimulants, including bradykinin (BK), can induce increase in [Ca(2+)](i) in PC12 cells. Bradykinin induces an increase in [Ca(2+)](i) via intracellular Ca(2+) release and extracellular Ca(2+) 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 Ca(2+) release and extracellular Ca(2+) influx, and further studied the mechanism of glucocorticoid's action. To dissociate the intracellular Ca(2+) release and extracellular Ca(2+) influx induced by BK, the Ca(2+)-free/Ca(2+)- reintroduction protocol was used. The results were as follows: (1) The Ca(2+) influx induced by BK could be rapidly inhibited by Cort, but intracellular Ca(2+) release could not be affected significantly. (2) The inhibitory effect of Cort-BSA (BSA -conjugated Cort) on Ca(2+) 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 Gö6976 could reverse the inhibitory effect of Cort. (4) There was no inhibitory effect of Cort on Ca(2+) 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 Ca(2+) influx induced by BK through the pertussis toxin -sensitive G protein-PKC pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bradykinin / antagonists & inhibitors*
  • Bradykinin / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Carbazoles / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Proteins / metabolism
  • Glucocorticoids / pharmacology*
  • Indoles / pharmacology
  • PC12 Cells
  • Pertussis Toxin / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Rats
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thapsigargin / pharmacology
  • omega-Conotoxins / pharmacology


  • Calcium Channel Blockers
  • Carbazoles
  • Enzyme Inhibitors
  • Glucocorticoids
  • Indoles
  • omega-Conotoxins
  • Go 6976
  • Thapsigargin
  • Pertussis Toxin
  • Protein Kinase C
  • GTP-Binding Proteins
  • Tetradecanoylphorbol Acetate
  • Bradykinin
  • Calcium