| Project/Area Number |
18590242
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Toho University |
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Principal Investigator |
KOIKE Katsuo Toho University, Faculty of Pharmaceutical Sciences, Professor (70147578)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Yoshio Toho University, Faculty of Pharmaceutical Sciences, Associate Professor (60188349)
MICHIKAWA Hiromi Toho University, Faculty of Pharmaceutical Sciences, Lecturer (00277477)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,650,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | β-adrenocentors / vascular smooth muscle / relaxant response / β3-adrenocentors / atenolol / ICI-118,551 / cyclic AMP / potassium channel / ラット血管平滑筋 / 胸部大動脈 / ブプラノロール / プロプラノロール |
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| Research Abstract |
β-Adrenoceptors ((β-ARs) are now classified into three subtypes : β1, β2 and (β3. Of these three subtypes, β3-AR was first identified in fat tissue and its distribution and role in smooth muscles were not well known. However, we have recently found that (β3-AR is abundantly present in gastrointestinal smooth muscles and plays the key role in their relaxant responses to endogenous catecholamines. In the present study, we investigated the expression and post-receptor mechanisms of β3-AR as well as non-β3-ARs ((β1- and β2-ARs) in rat aortic smooth muscle for our better understating of the vascular smooth muscle β-ARs, and we obtained the following new findings and/or established experimental conditions.
1. We established the evaluation system to detect β-AR-mediated vascular smooth muscle relaxation.
2. We found that isoprenaline (ISO)-induced relaxation is mediated through propranolol (Prop)-sensitive β-AR and Prop-insensitive β-AR.
3. Based on the rank order of the relaxant potencies of three catecholamines and the pA2 values of subtype-selective β-AR antagonists (atenolol and ICI-118,551) against ISO, we found that Prop-sensitive β-AR is mainly β2-AR in thoracic aorta and it is β1-AR in abdominal aorta.
4. Based on the, pA2 value of bupranolol against ISO, we found that Prop-insensitive β3-AR is mainly β3-AR in both thoracic and abdominal aortae.
5. We found that mRNAs and receptor proteins corresponding to each β-AR are expressed in the vascular smooth muscles used in the above mechanical studies.
6. We found that β3-AR-mediated vascular relaxation is trigged by new molecular mechanisms (cAMP-independent mechanisms and contribution of voltage-dependent potassium channel).
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