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 Gö6976. When PC12 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.
Qiu
J
J
Neuroscience Research Institute, Second Military Medical University, Shanghai Institute of Physiology, China.
Lou
L G
LG
Huang
X Y
XY
Lou
S J
SJ
Pei
G
G
Chen
Y Z
YZ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003348:Cortisone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016678:Genome; D007425:Intracellular Membranes / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D009994:Osmolar Concentration; D016716:PC12 Cells / Q000378:metabolism; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010566:Virulence Factors, Bordetella; D012710:Serum Albumin, Bovine; D009538:Nicotine; D037342:Pertussis Toxin; D011493:Protein Kinase C; D002118:Calcium; D003348:Cortisone