Chlorpromazine inhibits store-operated calcium entry and subsequent noradrenaline secretion in PC12 cells.
1. The effect of chlorpromazine on the store-operated Ca2+ entry activated via the phospholipase C signalling pathway was investigated in PC12 cells. 2. Chlorpromazine inhibited the sustained increase after the initial peak in the intracellular Ca2+ concentration produced by bradykinin while having no effect on the initial transient response. The inhibition was lowered by the removal of extracellular free Ca2+. However, chlorpromazine did not inhibit bradykinin-induced inositol 1,4,5-trisphosphate production. 3. Chlorpromazine inhibited the bradykinin-induced noradrenaline secretion in a concentration-dependent manner (IC(50): 24+/-5 microM, n=3). 4. To test for a direct effect of chlorpromazine on store-operated Ca2+ entry, thapsigargin, an inhibitor of microsomal Ca(2+)-ATPase, was used to induce store-operated Ca2+ entry in PC12 cells. Chlorpromazine reduced the thapsigargin-induced sustained Ca2+ level (IC(50): 24+/-2 microM, n=3), and the inhibition also occluded the inhibitory action of 1-[-[3-(4-methoxyphenyl) propoxy]-4-methoxyphenyl]-1H-imidazole hydrochloride (SK&F96365). 5. The results suggest that chlorpromazine negatively modulates the store-operated Ca2+ entry activated subsequent to PLC activation.
Choi
S Y
SY
Department of Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea.
Kim
Y H
YH
Lee
Y K
YK
Kim
K T
KT
D000465:Algorithms; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002746:Chlorpromazine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D007093:Imidazoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008345:Manganese / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology
D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007093:Imidazoles; D008345:Manganese; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; D016257:Fura-2; D002746:Chlorpromazine; D009638:Norepinephrine