Differential inhibition of Na+/Ca2+ exchanger isoforms by divalent cations and isothiourea derivative
Differential inhibition of Na+/Ca2+ exchanger isoforms by divalent cations and isothiourea derivative
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DOI：
10.1152/ajpcell.1998.275.2.c423
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发表时间：
1998-08-01
影响因子：
5.5
通讯作者：
Shigekawa, M
中科院分区：
文献类型：
--
作者：
Iwamoto, T;Shigekawa, M
我们通过分析Ni 2+和其他阳离子以及最近鉴定的抑制剂异噻唑烷衍生物对稳定表达每种亚型的CCL-39（Dede）成纤维细胞的细胞内Na+依赖性Ca-45（2+）摄取的影响，比较了三种哺乳动物Na+/Ca 2+交换亚型NCX 1、NCX 2和NCX 3的性质。所有这些NCX异构体对细胞外转运底物Ca 2+和Na+的亲和力相似。Ni 2+通过与Ca 2+竞争外转运位点抑制Ca-45（2+）的摄取，在NCX 3中的亲和力比在NCX 1或NCX 2中低10倍。Ni ~（2+）和Co ~（2+）对NCX亚型的抑制作用最强，但其抑制活性低于La ~（3+）和Cd ~（2+）。一价阳离子Li+刺激所有NCX亚型的Ca-45（2+）摄取速率相似，亲和力低，尽管刺激程度在NCX 1中略小。另一方面，异噻唑烷衍生物KB-R7943对NCX 3的抑制性是对NCX 1或NCX 2的3倍。因此，在NCX 3和其他两种亚型之间检测到动力学和药理学性质的明显差异。
We compared the properties of three mammalian Na+/Ca2+ exchanger isoforms, NCX1, NCX2, and NCX3, by analyzing the effects of Ni2+ and other cations as well as the recently identified inhibitor isothiourea derivatives on intracellular Nai-dependent Ca-45(2+) uptake into CCL-39 (Dede) fibroblasts stably expressing each isoform. All these NCX isoforms had similar affinities for the extracellular transport substrates Ca2+ and Na+.Ni2+ inhibited Ca-45(2+) uptake by competing with Ca2+ for the external transport site, with 10-fold less affinity in NCX3 than in NCX1 or NCX2. Ni2+ and Co2+ were most efficient in such discrimination of NCX isoforms, although their inhibitory potencies were less than those of La3+ and Cd2+. The monovalent cation Li+ stimulated Ca-45(2+) uptake rate by all NCX isoforms similarly with low affinity, although the extent of stimulation was somewhat smaller in NCX1. On the other hand, the isothiourea derivative KB-R7943 was threefold more inhibitory to NCX3 than to NCX1 or NCX2. Thus distinct differences in the kinetic and pharmacological properties were detected between NCX3 and the other two isoforms.