| Project/Area Number |
22592077
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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 |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
YAMADA Shoji 昭和大学, 歯学部, 教授 (00111617)
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| Co-Investigator(Kenkyū-buntansha) |
AMANO Hitoshi 昭和大学, 歯学部, 准教授 (90212571)
唐川 亜希子 昭和大学, 歯学部, 助教 (70552280)
竹田 秀 慶應義塾大学, 医学部, 准教授 (30376727)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 破骨細胞 / アドレナリン / β2作動薬 / β２受容体 / 骨吸収 / 自律神経 / 骨代謝 / 骨粗鬆症 / 骨粗鬆症治療薬 / β2受容体 / 交感神経 / 光学異性体 / 自律神経系 |
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| Research Abstract |
When (-)-(R)- and (+)-(S)-enantiomers of ・2-adrenergic receptor (β2-AR) agonist tulobuterol (each 10 mg/kg) was subcutaneously injected into female young rats once a day for 4 weeks, the effects of each enantiomer on the muscle and bone were examined. The (-)-(R)-enantiomer, but not (+)-(S)-enantiomer, significantly increased the body weight and decreased fat, compared with vehicle control. Particularly, the (R)-enantiomer not only increased the heart muscle and skeletal muscle but shifted the muscle lactate dehydrogenase (LDH) isoenzyme from the H-type to M-type and also myosin heavy chain (HMC) isoform pattern from slow type to fast type. On the other hand, the (S)-enantiomer decreased the bone mineral density, accompanied with increase in urinary deoxypyridinoline excretion. In vitro, osteoclast-like cell formation were generated in co-culture, mouse bone marrow cells (BMC) and ST2-T cells preparations for 7 days, treated with (S)-enantiomer more than with (R)-enantiomer. Moreover, it was inhibited by selective β2-AR inhibitor butoxamine and non-selective β-AR inhibitor propranolol. The effects of (R)-enantiomer of β2-AR agonist should be convenient for athletes and exercisers, but the (S)-enantiomer might influence the bone growth and increase the risk of bone fracture in young users, in particular when used illegal dosage as doping. This study is the first report indicating the different activities of (R)- and (S)-enantiomers of β2-AR agonist on the muscle and bone. We need to carry out “racemiswitch” to develop drugs consisting useful active enantiomer.
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