Knockout Mice for Pharmacological Screening: Testing the Specificity of Na+-Ca2+ Exchange Inhibitors

H. Reuter, S. Henderson, T. Han, T. Matsuda, A. Baba, R. Ross, J. Goldhaber, K. Philipson
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引用次数: 146

Abstract

The role of the Na+-Ca2+ exchanger as a major determinant of cell Ca2+ is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to electrically stimulated heart tubes from control mouse embryos or embryos with the Na+-Ca2+ exchanger knocked out. We monitored effects of the drugs on Ca2+ transients. Both drugs depress the Ca2+ transients at low concentrations even in the absence of any Na+-Ca2+ exchanger. KB-R7943 and SEA0400 are not completely specific and should be used with caution as Na+-Ca2+ exchange inhibitors.
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基因敲除小鼠的药理学筛选:测试Na+-Ca2+交换抑制剂的特异性
在心脏组织中,Na+-Ca2+交换剂作为细胞Ca2+的主要决定因素的作用是明确的,并且已经努力开发特异性抑制剂的交换剂。我们使用一种新的系统来测试两种假定的特异性抑制剂KB-R7943和SEA0400的特异性。这些药物被应用于来自对照小鼠胚胎或Na+-Ca2+交换器被敲除的胚胎的电刺激心脏管。我们监测了药物对Ca2+瞬态的影响。即使在没有任何Na+-Ca2+交换剂的情况下,这两种药物也会在低浓度下抑制Ca2+瞬态。KB-R7943和SEA0400不是完全特异性的,作为Na+-Ca2+交换抑制剂应谨慎使用。
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