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中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (1): 35-38.

• 研究原著 • 上一篇    下一篇

盐酸埃他卡林对动脉平滑肌ATP 敏感性钾通道与其开放剂[3H] P1075 特异性结合与解离动力学过程的影响

龙超良, 何华美, 汪海   

  1. 军事医学科学院毒物药物研究所, 北京 100850
  • 收稿日期:2003-06-13 修回日期:2003-07-03 出版日期:2004-01-26 发布日期:2020-11-16
  • 作者简介:龙超良, 男, 医学博士, 助理研究员, 主要从事心血管药理学研究。汪海, 男, 研究员, 博士生导师, 主要从事心血管药理和新药研究。Tel:010-66932651  Fax: 010-68211656  E-mail: wh@nic.bmi.ac.cn。前两位作者对本文的贡献相同。
  • 基金资助:
    国家新药研究与发展重点项目(NO.969010101); 国家“ 863 计划” 重大专项(NO.2002AA2Z3137)

Effects of iptakalim hydrochloride on association and dissociation kinetic processes of [3H] P1075 binding with ATP-sensitive potassium channels in artery smooth muscles

LONG Chao-Liang, HE Hua-Mei, WANG Hai   

  1. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
  • Received:2003-06-13 Revised:2003-07-03 Online:2004-01-26 Published:2020-11-16

摘要: 目的: 研究盐酸埃他卡林(iptakalim hydrochloride, Ipt) 对[3H] P1075 与血管平滑肌ATP 敏感性钾通道(ATP-sensitive potassium channel, KATP) 结合和解离动力学过程的影响。方法: KATP 开放剂[3H] P1075与大鼠去内皮主动脉平滑肌特异性结合与解离的动力学试验。结果: Ipt 预先与主动脉平滑肌孵育后,[3H] 1075 的结合速率减慢, 结合幅度降低, 平衡结合常数KA 降为对照组的28.3 %(P<0.01);结合[3H] P1075 的解离速率增快, 解离幅度增加, 平衡解离常数KD 则较对照组增加3.53 倍(P<0.01) 。在相同条件下, KATP开放剂吡那地尔(pinacidil, Pin) 的作用与之相似, KA值降为对照组的35 %(P<0.01),KD 值较对照组增加2.88 倍(P<0.01) 。结论: Ipt与KATP开放剂Pin的作用相似, 两者均可变构调节KATP,抑制其与开放剂的结合过程, 促进其解离过程。

关键词: 盐酸埃他卡林, 吡那地尔, [3H] P1075, ATP敏感性钾通道, 硫脲受体

Abstract: AIM: To investigate the effects of iptakalim hydrochloride (Ipt) on the association and dissociation kinetic processes of [3H] P1075 binding with sulfonylurea receptor (SUR) of ATP-sensitive potassium channel (KATP) in artery smooth muscles derived from Wistar rats.METHODS: The experiments of the association and dissociation kinetic processes of KATP opener [3H] P1075 binding with endothelium-denuded aorta smooth muscles were used.RESULTS: When artery smooth muscle preparations were preincubated with Ipt 100 μmol·L-1, the association kinetic processe of [3H]P1075 binding with SUR was retarded.The apparent association rate constant (KA) of [3H] P1075 binding with SUR was 28.3 % as much as that of control group (P<0.01).The dissociation kinetic processes of bounded [3H] P1075 with SUR was accelerated.The apparent dissociation rate constant (KD) were 3.53-fold as much as that of control group (P<0.01).Under the same experimental conditions, the effects of KATP opener Pin were similar with those of Ipt.The values of KA and KD were 35 % and 2.88-fold as much as those of control group (P<0.01).CONCLUSION: The effects of Ipt are similar with those of KATP opener Pin.Both of them have allosteric modulatory effects on KATP.They can inhibit the association kinetic processes and accelerate the dissociation kinetic processes of openers binding with KATP.

Key words: iptakalim hydrochloride, pinacidil, [3H] P1075, ATP-sensitive potassium channel, sulfonylureareceptor

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