Calmidazolium chloride is a very potent inhibitor of several Ca2+-calmodulin-dependent enzymes, the IC50 values are 0.01μM for brain phosphodiesterase, 0.2μM for erythrocyte Ca2+-ATPase and 5.0μM for phosphorylase b kinase [1]. Calmidazolium chloride is a kind of derivative of the antimycotic miconazole, and proposed as a more specific and useful tool for studying the involvement of calmodulin in biological processes [1].
Calmidazolium chloride (4nM; 1h) inhibited activity of calmodulin (CaM) in Aeromonas hydrophila-induced head kidney macrophage (HKM) [2]. Calmidazolium chloride (5μM) decreased the Ca2+ current in mouse pancreatic β-cells; Calmidazolium chloride (5μM; 10min) stimulated insulin release from mouse pancreatic β-cells [3].
Calmidazolium chloride (3.75µg; i.p.) significantly decreased the level of the phosphodiesterase 1 (PDE1) in damaged muscles of C57BL/6 mice induced by cardiotoxin; Calmidazolium chloride (3.75µg; i.p.) increased the expression of TGF-β2 and IL-10 and down-regulated the mRNA levels of pro-inflammatory TNF-α and IL-6 in CD45+ cells in damaged muscles of C57BL/6 mice induced by cardiotoxin [4].
References:
[1] Van Belle H. R 24 571: A potent inhibitor of calmodulin-activated enzymes [J]. Cell Calcium, 1981, 2(5): 483-494.
[2] Banerjee C, Khatri P, Raman R, et al. Role of calmodulin-calmodulin kinase II, cAMP/protein kinase A and ERK 1/2 on Aeromonas hydrophila-induced apoptosis of head kidney macrophages [J]. PLoS Pathog, 2014, 10(4): e1004018.
[3] Kindmark H, Køohler M, Larsson O, et al. Dissociation between exocytosis and Ca2+-channel activity in mouse pancreatic β-cells stimulated with calmidazolium (compound R 24571) [J]. FEBS letters, 1995, 369(2-3): 315-320.
[4] Hu J, Shi D, Ding M, et al. Calmodulin-dependent signalling pathways are activated and mediate the acute inflammatory response of injured skeletal muscle [J]. The Journal of physiology, 2019, 597(21): 5161-5177.
Calmidazolium chloride是一种高效的Ca2+钙调蛋白依赖性酶抑制剂，其抑制脑磷酸二酯酶、红细胞Ca2+-ATP酶和磷酸化酶b激酶的IC50值分别为0.01μM、0.2μM和5.0μM[1]。Calmidazolium chloride是一种抗真菌药物咪康唑的衍生物，是研究钙调蛋白参与生物过程的一种更特异和有用的工具[1]。
Calmidazolium chloride（4nM；1h）抑制Aeromonas hydrophila感染的HKM（head kidney macrophage）中钙调蛋白的活性[2]。Calmidazolium chloride（5μM）降低小鼠胰岛β细胞中的Ca2+电流；Calmidazolium chloride（5μM；10min）刺激小鼠胰岛β细胞释放胰岛素[3]。
Calmidazolium chloride（3.75µg；i.p.）显著降低心脏毒素诱导的C57BL/6小鼠损伤肌肉中的磷酸二酯酶1的水平；Calmidazolium chloride（3.75µg；i.p.）增加心脏毒素诱导C57BL/6小鼠损伤肌肉中TGF-β2和IL-10的表达，下调促炎因子TNF-α和IL-6 mRNA水平[4]。