Chlorpromazine inhibits store‐operated calcium entry and subsequent noradrenaline secretion in PC12 cells

The effect of chlorpromazine on the store‐operated Ca 2+ entry activated via the phospholipase C signalling pathway was investigated in PC12 cells. Chlorpromazine inhibited the sustained increase after the initial peak in the intracellular Ca 2+ concentration produced by bradykinin while having no effect on the initial transient response. The inhibition was lowered by the removal of extracellular free Ca 2+ . However, chlorpromazine did not inhibit bradykinin‐induced inositol 1,4,5‐trisphosphate production. Chlorpromazine inhibited the bradykinin‐induced noradrenaline secretion in a concentration‐dependent manner (IC 50 : 24±5 μ M , n =3). To test for a direct effect of chlorpromazine on store‐operated Ca 2+ entry, thapsigargin, an inhibitor of microsomal Ca 2+ ‐ATPase, was used to induce store‐operated Ca 2+ entry in PC12 cells. Chlorpromazine reduced the thapsigargin‐induced sustained Ca 2+ level (IC 50 : 24±2 μ M , n =3), and the inhibition also occluded the inhibitory action of 1‐[‐[3‐(4‐methoxyphenyl) propoxy]‐4‐methoxyphenyl]‐1H‐imidazole hydrochloride (SK&F96365). The results suggest that chlorpromazine negatively modulates the store‐operated Ca 2+ entry activated subsequent to PLC activation.British Journal of Pharmacology (2001) 132 , 411–418; doi: 10.1038/sj.bjp.0703840