盐酸埃他卡林对[~3H]格列本脲与动脉平滑肌K_(ATP)结合和解离动力学过程的影响以及与核苷酸的交互作用

目的　研究盐酸埃他卡林 (Iptakalimhydrochloride,Ipt)对 3 H]格列本脲 (glibenclamide,Gli)与大鼠血管平滑肌ATP敏感性钾通道 (ATP sensitivepotassiumchannel,KATP)的硫脲受体(Sulfonylureareceptor,SUR2B)结合和解离动力学过程的影响 ,并比较其作用特点与核苷酸类物质的异同点及它们之间的交互效应。方法　KATP拮抗剂 3 H]Gli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　 (1 )在浓度为 1 0pmol·L-1 ～ 0 5mmol·L-1 范围内 ,Ipt不能取代SUR2B与 3 H]Gli2 0 0 3 0 616收稿 ,2 0 0 3 112 5修回 国家新药研究与发展重点项目 ,No 9690 10 10 1;国家“863”计划重大专项 ,No 2 0 0 2AA2Z3 13 7作者简介 :何华美 ,男 ,3 6岁 ,博士 ,副教授。研究方向 :心血管药理学。E mail:longchaoliang @sohu .com ;汪　海 ,男 ,40岁 ,研究员 ,博士生导师。研究方向 :心血管药理和新药。通讯作者。Tel :86 10 6693 2 65 1,Fax:86 10 682 1165 6,E mail:wh @nic.bmi.ac .cn之间的特异性结合。Ipt 1 0 0 μmol·L-1 调节 3 H]Gli与SUR2B特异性结合的动力学过程的特征为抑制其结合动力学过程 ,使其结合速率减慢 ,结合幅度降低 ;促进其解离动力学过程 ,使其解离速率加快 ,解离幅度增加。 (2 )ATP

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

AIM To investigate the effects of iptakalim hydrochloride(Ipt) on the association and dissociation kinetic processes of 3H]glibenclamide(Gli) binding with sulfonylurea receptor(SUR 2B ) of ATP sensitive potassium channel (K ATP ) in vascular smooth muscles derived from Wistar rats,and to compare the properties of Ipt with those of nucleotides. The interactions between Ipt and nucleotides were also determined. METHODS The experiments of the association and dissociation kinetic processes of K ATP blocker 3H]Gli binding with endothelium denuded aorta smooth muscles were used. RESRLTS (1)The specific bindings of 3H]Gli with SUR 2B were not displaced by Ipt at the concentrations of 10 pmol·L -1 ～ 0 5 mmol·L 1 . Ipt 100 μmol·L -1 retarded the association kinetic process and accelerated the dissociation kinetic process of 3H]Gli binding with SUR 2B . (2)Opposite to Ipt, ATP 1 mmol·L -1 accelerated the association kinetic process and retarded the dissociation kinetic process of 3H]Gli binding with SUR 2B There was an interaction between ATP and Ipt in the modulation of 3H]Gli binding with SUR 2B . (3) Similar with Ipt, ADP 1 mmol·L -1 retarded the association kinetic process and accelerated the dissociation kinetic process of 3H]Gli binding with SUR 2B , there was an interaction between ADP and Ipt in the modulation of 3H]Gli binding with SUR 2B . (4)Different from ATP and ADP, UDP had no effect on the association and dissociation kinetic process of 3H]Gli binding with SUR 2B . And there was not interaction between UDP and Ipt. CONCLUSION Ipt had no affinity with the binding sites of K ATP blocker in SUR 2B , but had negative allosterical modulation on it. The modulatory properties of Ipt were opposite to those of ATP, similar with those of ADP and different from those of UDP. There were interactions between ATP, ADP and Ipt in the modulation of 3H]Gli binding with SUR 2B , but there was not interaction between UDP and Ipt.