Elucidation of the molecular mechanism underlying the regulation of vascular smooth muscle-type ATP-sensitive K+ channels by modification of phosphorylation
| Project/Area Number |
18K15030
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48030:Pharmacology-related
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| Research Institution | Saga University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 薬理学 / 血管平滑筋 / イオンチャネル / ATP感受性カリウムチャネル / リン酸化修飾 / GLP-1受容体作動薬 / シグナル伝達 |
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| Outline of Final Research Achievements |
In this study, we examined the modification of phosphorylation of vascular smooth muscle-type ATP-sensitive K+ (KATP) channels by administering glucagon-like peptide-1 (GLP-1) receptor agonists.
In an isotonic contraction experiment using smooth muscle cells of mouse portal vein, administration of GLP-1 (7-36) amide showed a concentration-dependent suppression of spontaneous muscle contraction and subsequent induction of a relaxation response. However, this relaxation response was suppressed upon administration of glibenclamide. Similar responses were observed when other GLP-1 receptor agonists such as exendin-4 or liraglutide were administered.
These results strongly suggested that GLP-1 receptor agonists activate vascular smooth muscle-type KATP channels.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、血管平滑筋に関する研究領域において分子生物学的手法および免疫組織化学染色法を用いた『形態学的解析』のみならず、細胞内cAMP動態計測法および電気生理学的手法を用いた『機能学的解析』を行っている研究グループは国内外で非常に少ない。本研究にて血管平滑筋型KATPチャネルにおけるリン酸化によるチャネル修飾機序が明らかになる意義は大きいと考えられる。
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Report
(3 results)
Research Products
(2 results)
