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Human alpha_<1a>-adrenoceptor polymorphism : Association with benign prostate hyperplasia

Research Project

Project/Area Number 09671613
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionNiigata University

Principal Investigator

HATANO Akihiko  Niigata University School of Medicine Assistant, 医学部, 助手 (00242404)

Co-Investigator(Kenkyū-buntansha) TSUTSUI Toshiki  Niigata Univ.Med.Hosp., Assistant, 医学部附属病院, 助手 (20283012)
TAKEDA Masayuki  Niigata Univ.School of Medicine, Associate Professor, 医学部, 助教授 (80197318)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsHuman / Benign prostate hyperplasis / alpha_<1a>-Adrenoceptor / Polymorphism / α_<LA>-アドレナリン受容体
Research Abstract

Molecular cloning identified three distinct cDNAs encoding alpha_1-adrenoceptors (alpha_<1a>, alpha_<1b>, and alpha_<1d>). Among subtypes, human prostate has been shown to express predominantly alpha_<1a>-adrenoceptors, and these mediate the contractile response. It is already known that two restriction fragment length poylmorphisms (RFLPs) of alpha_<1a>-adrenoceptor gene digested with Pst I restriction enzyme exist in human. This polymorphism might confer an additional putative palmitoylation site in the carboxy-terminal segment of alpha_<1a>-adrenoceptor, implying abnormal signal transduction mechanism. Also, mutation in the third cytoplas-mic loop of alpha_<1a>-adrenoceptor might induce the constitutive activation of the receptor/signal transduc-tion. In the present study, we looked for a possible mutation in the third intracellular loop of the alpha_<1a>-adrenoceptor gene. Fresh prostate tissues were obtained at the time of surgery from 27 patients, frozen in liquid nitrogen, and s … More tored at -80゚C.Total RNA was extracted from the prostate tissue, then reverse transcribed, and cDNA was prepared. Fragments of PCR products which encodes the third intracellular loop of alpha_<1a>-adrenoceptor were purified and analysed by DNA sequencer. As a result, no mutation in the third cytoplasmic loop of the alpha_<1a>-adrenoceptor gene was observed. Additionary, we examined whether the Pst I-RFLP of the alpha_<1a>-adrenoceptor is associated with female urethral syndrome. PCR product of 502 bp, which contains the DNA sequence corresponding to Arg492, has been amplified from genomic DNA, and 2 RFLPs of alpha_<1a>-adrenoceptor gene, which are digested with Pst I restriction enzyme into 477bp and 25 bp, were cheked in middle aged women of either control or urethral syndrome. The frequency of alpha_<1a>-adrenoceptor polymorphism was not differently distributed between patients with urethral syndrome and normal subjects in Japan. However, the frequency distribution of this polymorphism was significantly different between normal Japanese and U.S.populations. Our preliminary study does not provide any evidence to support an association between alpha_<1a>-adrenoceptor gene polymorphism and fern ale ure-thral syndrome, however, much larger studies of both Japan and U.S.are needed. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Masayuki Takeda: "13th IUPHAR official satellite symposium : α_1-adrenoceptors as targets for therapeutic agents in urology : α_1- and α_2-adrenoceptors in BPH" European Urology. (印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Takeda: "Evidence for β_3-adrenoceptor subtypes in relaxation of the human urinary blad-der detrusor : analysis by molecular biological and phrmacological methods" Journal of pharmacology and experimental therapeutics. 288(3)印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takako Okamoto-Koizumi: "Pharmacological and molecular biological evidence for ET_A endothelin receptor subtypemedi-ating mechanical responses in the detrysor smooth muscle of the human urinary bladder" Clinical Science. 96. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Takeda: "Bladder neck suspension using percutaneous bladder neck stabilization to to the pubic bone with a bone-anchor suture fixation system : a new extraperitoneal laparoscopic approach" Urologia Internationalis. 848(印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Takeda, Akihiko Hatano, Kei Arai, Kenji Obara, Toshiki Tsutsui and Kota Takahashi: "13th IUPHAR official satellite symposium : alpha_1-adrenoceptors as targets for therapeutic agents in urology : alpha_1-and alpha_2-adrenoceptors in BPH" European Urology. Suppl. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Takeda, Kenji Obara, Takaki Mizusawa, Yoshihiko Tomita, Kei Arai, Toshiki Tsutsui, Akihiko Hatano, Kota Takahashi and Shintaro Nomura: "Evidence for beta_3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor : analysis by molecular biological and phrmacological methods" Journal of pharmacology and experimental therapeutics. 288 (3) (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takako Okamoto-Koizumi, Masayuki Takeda, Takashi Komeyama, Akihiko Hatano, Makoto Tamaki, Takaki Mizusawa, Toshiki Tsutsui, Kenji Obara, Yoshihiko Tomita, Kei Arai and Kota Takahashi: "Pharmacological and molecular biological evidence for ET_A endothelin receptor subtype mediating mechanical responses in the detrysor smoothmuscle of the human urinary bladder." Clinical Science. 96 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Takeda, Akihiko Hatano, Shigenori Kurumada, Hitoshi, Syunji Wakatsuki, Hideto Go, Ryusuke Watanabe, Yoshihiko Tomita, Kota Takahashi: "Bladder neck suspension using prcutaneous bladder neck stabilization to to the pubic bone with a bone-anchor suture fixation system : a new extraperitoneal laparoscopic approach" Urologia Internationalis. 848 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masayuki Takeda: "13th IUPHAR official satellite symposium:α_1-adrenoceptors as targets for therapeutic agents in urology:α_1-and α_2-adrenoceptors in BPH" European Urology. (印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masayuki Takeda: "Evidence for β_3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor:analysis by molecular biological and phrmacological methods" Journal of pharmacology and experimental therapeutics. 288(3)(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takako Okamoto-Koizumi: "Pharmacological and molecular biological evidence for ET_A endothelin receptor subtype me-diating mechanical responses in the detrysor smooth muscle of the human urinary bladder" Clinical Science. 96(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masayuki Takeda: "Bladder neck suspension using percutaneous bladder neck stabilization to to the pubic bone with a bone-anchor suture fixation system:a new extraperitoneal laparoscopic approach" Urologia Internationalis. 848(印刷中). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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