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Urinary Incontinence and Mutation of β_3 Adrenoceptor Gene

Research Project

Project/Area Number 12470335
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionFukushima Medical University

Principal Investigator

YAMAGUCHI Osamu  Fukushima Medical University Schoolof Medicine, Department of Urology, Professor and Chairman, 医学部・泌尿器科, 教授 (60006814)

Co-Investigator(Kenkyū-buntansha) YOKOTA Takashi  Fukushima Medical University School of Medicine, Department of Urology, Associate Professor, 医学部・泌尿器科, 助教授 (20240939)
HASHIMOTO Tasturu  Fukushima Medical University School of Medicine, Department of Urology, Assistant, 医学部・泌尿器科, 助手 (70305374)
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥3,900,000 (Direct Cost: ¥3,900,000)
Keywordsβ_3-adrenoceptor / gene mutatation / overactive bladder / urge incontinence / cAMP / BKca channel / 尿失禁 / β3アドレナリン受容体 / β_3-アドレナリン受容体
Research Abstract

A miss-sense mutation in codon 64 of the β_3-adrenoceptor(AR) occurs with some frequency. Because activation of the β_3-AR causes a relaxation of detrusor muscle, we hypothesized that this mutation may be involved in idiopathic overactive bladder(OAB), leading to urge incontinence. The present study was therefore undertaken to investigate the above possibility.
We showed that the mRNA of α_<1a>,α_<1b>,α_<1d>, β_1 and β_2-AR was expressed at low levels, while β_3-AR was the most highly expressed subtype(approximately 94% of the overall messages) in human bladder. This predominant β_3-AR plays an essential role in relaxation of the bladder during urine storage.
We also investigated the mechanisms of relaxation via β_3-AR in detrusor muscle. Our results suggest that in addition to cAMP-dependent pathway, BKca channels are involved in the β_3-AR agonists-induced relaxation in pre-contracted detrusor muscle.
The studies, using CHO-K1 cells that express human β_3-AR and its mutant β_3AR, showed that there was no significant difference between wild type and mutation in terms of binding characteristics and cAMP production.
However, these findings can not be directly transferred to the in vivo situation.
Frinally, in large scale clinical study, we obtained hair root samples from 100 patients with idiopathic OAB and 101 non-OAB control volumteers. We found that the overall frequency of the β_3-AR gene mutation was 47% in the OAB patients, which was much higher than the mutation frequency of 22.8% in non-OAB control. These results provide support for our hypothesis that dysfunction of β_3-AR resulting from its gene mutation may be responsible for developing OAB symptoms. Thus, the β_3-AR polymorphism may be used as a genetic marker for OAB.

Report

(5 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (10 results)

All 2003 2002 Other

All Journal Article (8 results) Publications (2 results)

  • [Journal Article] A quantitative analysis of mRNA expression of α_1 and β-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders2003

    • Author(s)
      Nomiya M, Yamaguchi O
    • Journal Title

      THE JOURNAL OF UROLOGY 170

      Pages: 649-653

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] A quantitative analysis of mRNA expression of α_1 and β-adorenoceptor subtypes and their functional roles in human normnal and obstructed bladders2003

    • Author(s)
      Nomiya M, Yamaguchi O
    • Journal Title

      THE JOURNAL OF UROLOGY 170

      Pages: 694-653

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] β_3-Adrenoceptors in human detrusor muscle2002

    • Author(s)
      Yamaguchi Osamu
    • Journal Title

      UROLOGY 59

      Pages: 25-29

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] A quantitative analysis of α_1 and β-adorenoceptor subtypes mRNAs and their functional roles in human normal and obstructed bladders2002

    • Author(s)
      Nomiya M, Shishido K, Uchida H, Yamaguchi O
    • Journal Title

      NEUROUROLOGY AND URODYNAMICS 21

      Pages: 299-300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] β_3-adorenoceptors in human detrusor muscle2002

    • Author(s)
      Yamaguchi Osamu
    • Journal Title

      UROLOGY 59

      Pages: 25-29

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] A quantitative analysis of α_1 - and β-adorenoceptor subtypes mRNAs and their functional roles in human normal and obstructed bladders2002

    • Author(s)
      Nomiya M, Shishido K, Uchida H, Yamaguchi O
    • Journal Title

      NEUROUROLOGY AND URODYNAMICS 21(4)

      Pages: 299-300

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via β-adrenoceptors.

    • Author(s)
      Uchida H, Shishido K, Nomiya M, Yamaguchi O
    • Journal Title

      Eur J pharmacol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via β-adorenoceptors

    • Author(s)
      Uchida H, Shishido K, Nomiya M, Yamaguchi O
    • Journal Title

      Eur J pharmacol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Nomiya, O.yamaguchi: "A Quantitative analysis of mRNA Expression of α_1 and β-adorenoceptor subtypes and their functional roles in humannormaland obstructed bladders"Journal of Urology. 170. 649-653 (2000)

    • Related Report
      2003 Annual Research Report
  • [Publications] O.Yamaguchi: "β_3-Adrenoceptors in human detrusor muscle"Urology. 59,supp5A. 25-29 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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