Molecular and pharmacological investigation of ATP-sensitive K^+ channels in human detrusor

人逼尿肌 ATP 敏感 K^ 通道的分子和药理学研究

• 批准号: 14570080
• 负责人: TERAMOTO Noriyoshi
• 金额: $ 2.37万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570080/
• 关键词: Human detrusor smooth muscle; Unstable bladder; ATP-sensitive K^+ channels; Drugs for freauent micturition; Drugs for urinary incontinence; K^+ channel openers; カリウムチャネル; 電気生理学; 平滑筋; イオンチャネル; 治療薬

Recent molecular cloning studies have revealed that ATP-sensitive K^+ channels (K_<ATP> channels) are heteromeric complexes composed of at least two subunits, inwardly rectifying K^+ channels (Kir6.x) and sulphonylurea receptors (SURs). From functional expression experiments, pharmacological and electrophysiological studies have indicated that SUR1/Kir6.2 represents the pancreatic β-cell K_<ATP> channel, that SUR2A/Kir6.2 is thought to represent the cardiac K_<ATP> channel, whereas SUR2B/Kir6.1 may represent the vascular smooth muscle-type K_<ATP> channel.In the present experiments, we have investigated molecular and pharmacological properties of K_<ATP> channels in human urinary bladder smooth muscle. We have revealed that the pore region of Kir6.x in human urinary bladder-type K_<ATP> channels may mainly consist of Kir6.2 due to the results of Western blotting techniques. Furthermore, the subunits of SURs in human urinary bladder-type K_<ATP> channels are likely to be mixture of SUR1 and SUR2B.

最近的分子克隆研究表明，ATP敏感性钾通道（K_<ATP>channel）是由内向整流钾通道（Kir6.x）和磺脲受体（SURs）两个亚基组成的异聚体复合物。通过功能表达实验、药理学和电生理学研究表明，SUR 1/Kir6.2代表胰腺β细胞钾<ATP>通道，SUR 2A/Kir6.2代表心脏钾<ATP>通道，SUR 2B/Kir6.1代表血管平滑肌<ATP>钾通道<ATP>。Western印迹结果表明，人膀胱型钾通道中Kir6.x的孔区<ATP>可能主要由Kir6.2组成。膀胱型钾通道中SURs的亚基<ATP>可能是SUR 1和SUR 2B的混合物。

项目成果

TERAMOTO, N. et al.: "Multiple effects of mefenamic acid on K^+ currents in smooth muscle cells from pig urethra."British Journal of Pharmacology. 140. 1341-1350 (2003)

TERAMOTO, N. 等人：“甲芬那酸对猪尿道平滑肌细胞 K + 电流的多重影响。”英国药理学杂志。

Hirst G.D.S., Bramich N.J., Teramoo, N., Suzuki H., Edwards F.R.: "Regenerative component of slow waves in the guinea pig gastric antrum involves a delayed increase in [Ca^<2+>]_i and Cl^-channels"Journal of Physiology. 540. 907-919 (2002)

Hirst G.D.S.、Bramich N.J.、Teramoo, N.、Suzuki H.、Edwards F.R.：“豚鼠胃窦慢波的再生成分涉及 [Ca^2>]_i 和 Cl^ 通道的延迟增加”期刊

Teramoto, N.: "Molecular and electrophysiological investigation of ATP-sensitive K^+ channels in lower urinary tract function: the aims for clinical treatment of unstable detrusor."Folia Pharmacologica Japonica. 124. 317-324 (2003)

Teramoto, N.：“下尿路功能中 ATP 敏感 K^ 通道的分子和电生理学研究：不稳定逼尿肌的临床治疗目标。”Folia Pharmacologica Japonica。

寺本 憲功: "下部尿路機能の分子薬理学的及び電気生理学的解析研究 -尿失禁症の病態治療に向けて-"日薬雑誌. (印刷中). (2003)

Noriyoshi Teramoto：“下尿路功能的分子药理学和电生理学分析 - 尿失禁的病理治疗 -”Nichiyaku Zasshi（目前正在印刷）。

Teramoto, N.: "Interaction between inhibitory and excitatory metabotropic pathways in the guinea-pig antrum."Journal of Physiology. 550. 181-189 (2003)

Teramoto, N.：“豚鼠窦中抑制性和兴奋性代谢途径之间的相互作用。”生理学杂志。