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

Abstract

1 The eect of chlorpromazine on the store-operated Ca 2+ 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 Ca 2+ concentration produced by bradykinin while having no eect 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. 3 Chlorpromazine inhibited the bradykinin-induced noradrenaline secretion in a concentrationdependent manner (IC 50 : 24+5 mM, n=3). 4 To test for a direct eect 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 mM, 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 Ca 2+ entry activated subsequent to PLC activation.

Pharmacological modulation of monovalent cation currents through the epithelial Ca2+ channel ECaC1

“…The well described blocker of SOC‐ and TRP‐mediated Ca 2+ entry, SK&F 96365 (Choi et al ., 2001; Franzius et al ., 1994; Inoue et al ., 2001) was nearly ineffective on ECaC1 at concentrations up to 10 μ M (Figure 8A). In addition, other SOC blockers, such as the adenylcyclase inhibitor MDL 12330A and 2‐APB (van rossum et al ., 2000), did not remarkably affect the ECaC1‐mediated current.…”

The Effect of Therapeutic Blockades of Dust Particles‐Induced Ca2+ Signaling and Proinflammatory Cytokine IL‐8 in Human Bronchial Epithelial Cells

“…PM 10 -induced Ca 2+ increases were diminished by the combination treatment (Figures 5(d) and 5(f) ). To determine if CaM mediated TRPM2 activation, cells were treated with CLP, a Ca 2+ -CaM inhibitor [ 35 ]. CLP markedly inhibited PM 10 -induced Ca 2+ increase (Figures 5(e) and 5(f) , n = 114 cells).…”

Dos distúrbios psiquiátricos à antibioticoterapia: reposicionamento da clorpromazina como agente antibacteriano

“…As fenotiazinas inibem o transporte de cálcio (Ca 2+ ), impedindo a sua ligação às proteínas de ligação ao Ca 2+ , como a calmodulina [35]. Isto significa que os sistemas enzimáticos que são dependentes de Ca 2+ , tais como os envolvidos na geração de energia celular a partir da hidrólise de ATP, são inibidos [93].…”

“…Somado aos efeitos centrais clássicos produzidos pela inibição de receptores envolvidos na neurotransmissão, a CPZ também modula respostas dependentes de cálcio [35]. Assim como o haloperidol, a CPZ inibe a ligação do cálcio a calmodulina, tendo assim a capacidade de aumentar o tônus imunológico in vivo ao estimular a atividade linfocitária [36], além de ser associada a efeitos citotóxicos antineoplásicos [37].…”