Elucidation of the mechanisms underlying the regulation of ATP-sensitive K^+ channels by sulfonylureas
阐明磺酰脲类药物调节 ATP 敏感 K^ 通道的机制
基本信息
- 批准号:09671025
- 负责人:
- 金额:$ 2.3万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1997
- 资助国家:日本
- 起止时间:1997 至 1998
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
ATP-sensitive K^+(K_<ATP>) channels are key molecules which link the cell's metabolic status to its membrane potential. In pancreatic beta-cells, KK_<ATP> channel is not only a glucose sensor m insulin secretion but also a target for the insulin secretagogue, the sulfonylurea, widely used as oral hypoglycemic agents in the treatment of diabetes mellitus. In cardiac myocytes and neurons, K_<ATP> channels are supposed to be involved in cytoprotection in ischemia, We have shown that beta-cell K_<ATP> channel is a complex of the sulfonylurea receptor SURI and a newly cloned inward rectifier K_<ATP> channel member Kir6.2, and that cardiac myocyte K_<ATP> channel is a complex of the newly cloned sulfonylurea receptor SUR2 and the Kir6.2. Our purpose in this study is to clarify the molecular mechanisms underlying the regulation of K^+ channels.Sensitivities of the [3-cell (SUR1/Kir6.2) and cardiac (SUR2/Kir6.2) K_<ATP> channels to the sulfonylurea glibenclamide and the K_<ATP> channel opener … More diazoxide are different, and are determined by distinct SUR subunits. To determine the domains that confer glibenclamide and diazoxide sensitivities, we prepared a series of chimeras between SUR1 and SUR2, and studied the properties of the chimeric K_<ATP> channels. All chimeric SURs could generate currents when expressed in COS 1 cells with Kir6.2. Next, we have examined the effects of the glibenclamide and diazoxide on the chimeric currents measured as ^<86>Rb^+ efflux, and narrowed the region that confer the sensitivities to these reagents. Furthermore, we have constructed various chimeras between SUR1 and SUR2, and have almost determined the glibenclamide-responsive region by measuring the binding activities of @SH-labeled glibenclamide for the chimeras expressed in COS 1 cells (manuscript in 3@E1preparation).In addition, we have investigated the effects of G-protein on the reconstituted K_<ATP> channels. We have shown that G-protein alpha subunit directly regulates the K_<ATP> channel activity, and that the regulation is different between [3-cell (SUR1/Kir6.2) and cardiac (SUR2/Kir6.2) K_<ATP> channels, suggesting that the difference is determined by distinct SUR subunits. Less
ATP敏感性K^+(K_<ATP>)通道是连接细胞代谢状态与膜电位的关键分子。在胰岛β细胞中,KK_2<ATP>通道不仅是胰岛素分泌的葡萄糖传感器,而且是胰岛素促分泌剂磺酰脲类药物的作用靶点,磺酰脲类药物广泛用作口服降糖药治疗糖尿病。在心肌细胞和神经元中,K_<ATP>通道被认为参与了缺血时的细胞保护作用。我们发现β细胞K_<ATP>通道是磺酰脲类受体SURI和新近克隆的内向整流性K_通道成员Kir6.2的复合体<ATP>,心肌细胞K_<ATP>通道是新近克隆的磺酰脲类受体SUR 2和Kir6.2的复合体。本研究的目的是阐明钾通道调节的分子机制。[3]-细胞(SUR 1/Kir6.2)和心脏(SUR 2/Kir6.2)钾<ATP>通道对磺脲类药物格列本脲和钾<ATP>通道开放剂的敏感性 ...更多信息 二氮嗪是不同的,并由不同的SUR亚基决定。为了确定赋予格列本脲和二氮嗪敏感性的结构域,我们制备了一系列SUR 1和SUR 2之间的嵌合体,并研究了嵌合体K_通道的特性<ATP>。所有嵌合的SURs在含有Kir6.2的COS-1细胞中表达后均能产生电流。接下来,我们检测了格列本脲和二氮嗪对以^ Rb^+外排测定的嵌合电流的影响<86>,并缩小了对这些试剂敏感的区域。此外,我们还构建了SUR 1和SUR 2之间的嵌合体,并通过测定在COS 1细胞中表达的嵌合体与@ SH标记的格列本脲的结合活性,基本确定了格列本脲的反应区域(手稿在3@E1制备中),此外,我们还研究了G蛋白对重构的K通道的影响<ATP>。结果表明,G蛋白α亚基直接调节K<ATP>通道活性,且对[3-细胞](SUR 1/Kir6.2)和心脏(SUR 2/Kir6.2)K通道的调节作用不同<ATP>,提示这种差异是由不同的SUR亚基决定的。少
项目成果
期刊论文数量(29)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Inagaki, N.: "Diabetes mellitau and KATP channels" Diagnosis and Treatment. 86. 2085-2090 (1998)
Inagaki, N.:“糖尿病和 KATP 通道”诊断和治疗。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
稲垣暢也: "糖尿病とK_<ATP2>チャネル." 診断と治療. 86. 2085-2090 (1998)
Nobuya Inagaki:“糖尿病和 K_<ATP2> 诊断和治疗”。86。2085-2090 (1998)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Miki,T., Inagaki,N., et al.: "Abnormalities of pancreatic islets by targetted expression of dominant-negative K_<ATP> channel." Proc. Natl, Acad. Aci, USA.94. 11969-11973 (1997)
Miki,T.、Inagaki,N. 等人:“显性失活 K_<ATP> 通道的靶向表达导致胰岛异常。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
稲垣暢也: "ATP感受性K^+チャネル" 医学のあゆみ. 188. 309-313 (1999)
Nobuya Inagaki:“ATP 敏感 K^+ 通道”医学史 188. 309-313 (1999)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Inagaki, N.: "Molecular structure and function of KATP channels." Kidney and Dialysis. 45. 651-656 (1998)
Inagaki, N.:“KATP 通道的分子结构和功能。”
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- 影响因子:0
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INAGAKI Nobuya其他文献
気道熱傷の病態と治療、そして今後の展望について
呼吸道烧伤的病理学、治疗及未来展望
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
MANO Fumika;IKEDA Kaori;SATO Tosiya;NAKAYAMA Takeo;TANAKA Daisuke;JOO Erina;TAKAHASHI Yoshimitsu;KOSUGI Shinji;SEKINE Akihiro;TABARA Yasuharu;MATSUDA Fumihiko;INAGAKI Nobuya;Nagahama Study Group;田崎修 - 通讯作者:
田崎修
INAGAKI Nobuya的其他文献
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{{ truncateString('INAGAKI Nobuya', 18)}}的其他基金
Development of a noninvasive method for beta cell mass measurement using a nuclear magnetic resonance
开发使用核磁共振测量 β 细胞质量的无创方法
- 批准号:
25670258 - 财政年份:2013
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Development of the novel diagnostic method for quantification ofpancreatic beta-cell mass by magnetic resonance imaging
开发通过磁共振成像定量胰腺β细胞质量的新诊断方法
- 批准号:
22390185 - 财政年份:2010
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular Basis of Novel Membrane Transport Mechanism
新型膜传输机制的分子基础
- 批准号:
15GS0301 - 财政年份:2003
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Creative Scientific Research
Structure and physiological role of ATP-sensitive potassium channel
ATP敏感钾通道的结构和生理作用
- 批准号:
11470009 - 财政年份:1999
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of drugs which open or close ATP-sensitive KィイD1+ィエD1channels
开发打开或关闭 ATP 敏感 KiiD1+iED1 通道的药物
- 批准号:
10557002 - 财政年份:1998
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Cloning and functional characterization of inwardly rectifying K^+ channels expressed in pancreatic beta-cells
胰腺β细胞中表达的内向整流K^通道的克隆和功能表征
- 批准号:
07671107 - 财政年份:1995
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
相似海外基金
Assessment of role of Kir6.1 subunit (ATP-sensitive K+ channel) in J wave syndrome
Kir6.1 亚基(ATP 敏感 K 通道)在 J 波综合征中的作用评估
- 批准号:
26460334 - 财政年份:2014
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$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Promoting liver regeneration using an ATP-sensitive K+ channel opener
使用 ATP 敏感 K 通道开放剂促进肝脏再生
- 批准号:
25462077 - 财政年份:2013
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Functional role of ATP-sensitive K^+ channel in vascular endothelial cells
血管内皮细胞中ATP敏感性K^通道的功能作用
- 批准号:
20590249 - 财政年份:2008
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Role of mitochondrial ATP-sensitive K^+ channel in postconditioning
线粒体 ATP 敏感 K^ 通道在后处理中的作用
- 批准号:
20890037 - 财政年份:2008
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Young Scientists (Start-up)
Molecular and functional analysis of ATP-sensitive K^+ channel on the nuclear envelope
核膜上 ATP 敏感 K^ 通道的分子和功能分析
- 批准号:
18590232 - 财政年份:2006
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Interaction of sarcolemmal and mitochondrial ATP-sensitive K channel on cardioprotection
肌膜和线粒体 ATP 敏感 K 通道的相互作用对心脏保护作用
- 批准号:
15591636 - 财政年份:2003
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mitochondrial ATP-Sensitive K+ Channel in Heart
心脏中线粒体 ATP 敏感 K 通道
- 批准号:
6685153 - 财政年份:2002
- 资助金额:
$ 2.3万 - 项目类别:
Mitochondrial ATP-Sensitive K+ Channel in Heart
心脏中线粒体 ATP 敏感 K 通道
- 批准号:
6900969 - 财政年份:2002
- 资助金额:
$ 2.3万 - 项目类别:
Mitochondrial ATP-Sensitive K+ Channel in Heart
心脏中线粒体 ATP 敏感 K 通道
- 批准号:
6751996 - 财政年份:2002
- 资助金额:
$ 2.3万 - 项目类别:
The Mitochondrial ATP-Sensitive K+ Channel in Heart
心脏中线粒体 ATP 敏感 K 通道
- 批准号:
7762806 - 财政年份:2002
- 资助金额:
$ 2.3万 - 项目类别: