| Project/Area Number |
16380199
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Gifu University |
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Principal Investigator |
KOMORI Seiichi Gifu University, Faculty of Applied Biological Science, Professor, 応用生物科学部, 教授 (70195866)
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| Co-Investigator(Kenkyū-buntansha) |
UNNO Toshihiro Gifu University, Faculty of Applied Biological Science, Associate Professor, 応用生物科学部, 助教授 (90252121)
TANEIKE Tetsuro Rakuno Gakuen University, Department of Veterinary Medicine, Professor, 獣医学部, 教授 (30048110)
松山 勇人 岐阜大学, 応用生物科学部, 助手 (80345800)
源 宣之 岐阜大学, 応用生物科学部, 教授 (10144007)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2004: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Muscarinic receptor / M2 Subtype / M3 Subtype / Intestinal smooth muscle / Knockout mice / Cationic channel / Contractile response / Carbachol / 胃平滑筋 / 回腸平滑筋 / ムスカリン作動性収縮 / 非選択的陽イオンチャネル / Ca感受性Kチャネル / 電位依存性Ca電流 |
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| Research Abstract |
In the present study, we have used M_2 or M_3 single knockout (KO) and M_2/M_3-double KO mice as experimental tools, aiming to identify muscarinic signaling pathways leading to the contraction of intestinal smooth muscles and to elucidate the role of M_2 and M_3 receptors in the processes. The summarized results are as follows : 1) Analysis of the contractile responses to exogenously applied the muscarinic agonist carbachol or cholinergic nerve stimulation in ileal and gastric smooth muscles revealed that both M_2 and M_3 subtypes, via different signal transduction mechanisms, participate in mediating contractions with the latter subtype assuming a greater role (Unno et al., 2005 ; 2006 ; Kitazawa et al., 2007). 2) Using the patch clamp techniques, we have demonstrated that the activation of muscarinic cationic channels requires stimulation of both M_2 and M_3 subtypes in such a way that M_3 receptor permissively opens the channels, and M_2 receptor synergistically transmits the open state to a long-lasting mode (Okamoto et al., 2004 ; Sakamoto et al., 2006 ; Unno et al., 2006 ; Sakamoto et al., 2007). These results provide novel insights into the regulation of visceral smooth muscle cationic channel activity. 3) We have also studied the role of M_2 and M_3 subtypes in the regulations of voltage-gated Ca^<2+> channel activity, Ca^<2+> sensitivity to contractile proteins and peristaltic movement, and we are now preparing the manuscripts.
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