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Different effects of enantiomers of beta2-adrenergic agonist on muscle and bone.

Different effects of enantiomers of beta2-adrenergic agonist on muscle and bone.
β2-肾上腺素能激动剂对映体对肌肉和骨骼的不同影响。
批准号:
22592077
负责人:
YAMADA Shoji
金额:
$2.83万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2010
资助国家:
日本
项目状态:
已结题
起止时间:
2010 至 2012

项目摘要

项目成果

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中文摘要
翻译
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 examined. the (-)-(R)-enantiomerbut 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 musclelactate 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 densityaccompanied with increase in urinary deoxypyridinoline excretion.体外,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,inhibited by selective β2-AR inhibitor butoxamine and non-selective β-AR inhibitorpropranolol. The effects of (R)-enantiomer of β2-AR agonist should be convenient for athletes andexercisers,but the (S) enantiomer might influence the bone growth and increase the risk of bone fracture inyoung users,in particular when used illegal dosage as doping. This study is the first report indicating thedifferent activities of (R)- and (S)-enantiomers of β -AR agonist on the muscle and bone. We need tocarry out“racemiswitch”to develop drugs consisting useful active enantiomer。
英文摘要
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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会议论文
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DOI: --
发表时间: 2011
期刊:
影响因子: --
作者: [天野均, 府川有紀子, 脇能広, 唐川亜希子, 岡崎雅子, 臼井通彦, 竹田秀, 山本松男, 山田庄司, 宮本謙一]
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DOI: --
发表时间: 2010
期刊:
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DOI: --
发表时间: 2010
期刊: J Oral Bios 52
影响因子: --
作者: [Akiko Karakawa, Tsuneyoshi Sano, Hitoshi Amano, Shoji Yamada]
通讯作者: Shoji Yamada
MicroRNA-208 moauiates BMP-2-stimulated mouse preosteblast differentiation by directly targeting V-ets erythroblastosis virus E 26 oncogene homelog 1
MicroRNA-208 通过直接靶向 V-ets 成红细胞增多症病毒 E 26 癌基因同源基因 1 来增强 BMP-2 刺激的小鼠前成骨细胞分化
DOI: --
发表时间: 2010
期刊: J Biol Chem
影响因子: 4.8
作者: [Itoh, T., S.Takeda, Y.Akao]
通讯作者: Y.Akao
26
    Infrastructure Development for Historical Time-spatial Data Mning to Modern Japan
    Development of Data Mining Resources for Knowledge Discovery of Pre-Modern Japanese Concepts
    Effect of VEGF's on osteockast formation and activation
    • 批准号:
      13671950
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $1.86万
    • 财政年份:
      2001
    • 负责人:
      YAMADA Shoji
    • 依托单位:
    Developing a Historical Document Analysis System Using Hand-written OCR Techomology
    海外基金