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埃他卡林新衍生物激活ATP敏感性钾通道的亚型选择性 被引量：4

Selectivity of new iptakalim derivatives on the subtypes of ATP-sensitive potassium channels
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摘要 目的研究埃他卡林新衍生物对不同亚型KATP通道的选择性作用。方法在特异性表达Kir6.2/SUR1、Kir6.2/SUR2A、Kir6.1/SUR2B3种不同亚型KATP通道的HEK-293细胞模型上,分别给予0.1、1.0、10、100×10-6mol.L-1的埃他卡林新衍生物,研究其作用前后DiBAC4(3)细胞荧光强度的变化,评价其对克隆表达的不同亚型KATP通道的选择性作用。结果7个埃他卡林新衍生物可激活KATP通道,其中衍生物(3)、(7)、(8)、(9)、(12)和(14)对3个亚型的KATP通道均具有激活作用,衍生物(7)对Kir6.2/SUR2A亚型的激活作用最强;衍生物(6)纳他卡林(natakalim)仅激活Kir6.1/SUR2B亚型,对Kir6.2/SUR2A和Kir6.2/SUR1亚型均无激活作用。结论纳他卡林为Kir6.1/SUR2B亚型高选择性开放剂。 Aim To investigate the seletive actions of new iptakalim＇ s derivatives on different subtypes of ATP-sensitive potassium channels. Method In HEK- 293 cells expressing different recombinant KATP channels （Kir6.2/SUR1, Kir6.2/SUR2A and Kir6. 1/ SUR2B）, the selectivty of those novel derivatives on KATP channels were examined using fluorescence-based assays. Result In HEK-293 cells heterologously expressing Kit6. 2/SUR1, Kit6. 2/SUR2A and Kir6. 1/ SUR2B recombinant KATP channels, these compounds （3）, （7）, （8）, （9）, （12） and （14） at concentrationsof 0. 1, 1.0, 10, and 100 × 10-6 mol · L^-1. caused decreases in fluorescence responses using DiBAC4 （3）, while the compound （6） natakalim caused decreases in fluorescence responses for Kit6. 1/SUR2B recombinant KATP channels not for Kir6.2/SUR1 and Kit6.2/SUR2A recombinant KATP channels. Conclusion Natakalim showed high selectivity on the Kit6. 1/SUR2B subtype of KATP channels.
作者 陈玉萍 潘志远 崔文玉 汪海
机构地区 军事医学科学院毒物药物研究所 军事医学科学院卫生学环境医学研究所 北京赛德维康医药研究院
出处 《中国药理学通报》 CAS CSCD 北大核心 2008年第11期1427-1430,共4页 Chinese Pharmacological Bulletin
基金 国家高技术研究发展计划(863计划)重大专项基金资助(No2002AA2Z3137) 军队杰出人才资助项目(No06J023)
关键词 KATP通道 HEK-293细胞 纳他卡林 埃他卡林衍生物 KATP channels HEK-293 cells iptakalim＇ sderivatives natakalim
分类号 R329.2 [医药卫生—人体解剖和组织胚胎学] R329.24 [医药卫生—人体解剖和组织胚胎学]
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参考文献15

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共引文献15

同被引文献53

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中国药理学通报
2008年 第11期

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