Verapamil, a Ca2+ channel inhibitor acts as a local anesthetic and induces the sigma E dependent extra-cytoplasmic stress response in E-coli
Verapamil, a Ca2+ channel inhibitor acts as a local anesthetic and induces the sigma E dependent extra-cytoplasmic stress response in E-coli
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DOI：
10.1016/j.bbamem.2006.05.022
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发表时间：
2006-10-01
影响因子：
3.4
通讯作者：
Jacq, A.
中科院分区：
文献类型：
--
作者：
Andersen, C. L.;Holland, I. B.;Jacq, A.
维拉帕米在临床上用作Ca2+通道抑制剂，用于治疗心绞痛、高血压和心律失常等多种疾病。在这里，我们研究维拉帕米对大肠杆菌的影响。该药物在生长亚抑制浓度下可抑制细胞分裂，与 SOS 反应无关。我们证明维拉帕米是一种膜活性药物，与局部麻醉剂地布卡因具有相似的作用。因此，维拉帕米和地布卡因都消除了质子动力并降低了细胞内 ATP 浓度。这伴随着 degP 表达的诱导，这是 RpoE (SigmaE) 胞质外应激反应激活和 psp 操纵子激活的结果。维拉帕米作为一种膜活性化合物的这种作用可以解释其在真核细胞中的一般毒性。 (c) 2006 Elsevier B.V. 保留所有权利。
Verapamil is used clinically as a Ca2+ channel inhibitor for the treatment of various disorders such as angina, hypertension and cardiac arrhythmia. Here we study the effect of verapamil on the bacterium Escherichia coli. The drug was shown to inhibit cell division at growth sub inhibitory concentrations, independently of the SOS response. We show verapamil is a membrane active drug, with similar effects to dibucaine, a local anesthetic. Thus, both verapamil and dibucaine abolish the proton motive force and decrease the intracellular ATP concentration. This is accompanied by induction of degP expression, as a result of the activation of the RpoE (SigmaE) extra-cytoplasmic stress response, and activation of the psp operon. Such effects of verapamil, as a membrane active compound, could explain its general toxicity in eukaryotic cells. (c) 2006 Elsevier B.V. All rights reserved.