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Research ArticleArticle

Evidence for β3-Adrenoceptor Subtypes in Relaxation of the Human Urinary Bladder Detrusor: Analysis by Molecular Biological and Pharmacological Methods

Masayuki Takeda, Kenji Obara, Takaki Mizusawa, Yoshihiko Tomita, Kei Arai, Toshiki Tsutsui, Akihiko Hatano, Kota Takahashi and Shintaro Nomura
Journal of Pharmacology and Experimental Therapeutics March 1999, 288 (3) 1367-1373;
Masayuki Takeda
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Kenji Obara
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Takaki Mizusawa
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Yoshihiko Tomita
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Kei Arai
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Toshiki Tsutsui
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Akihiko Hatano
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Kota Takahashi
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Shintaro Nomura
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Abstract

The purpose of the present study was to confirm the presence of β3-adrenoceptor subtype in the relaxation of human urinary bladder detrusor tissue by reverse transcription-polymerase chain reaction (PCR); direct sequencing of the PCR product, in situ hybridization; and isometric contraction. Using reverse transcription-PCR, the mRNAs of three receptor subtypes (β1, β2, and β3) were expressed in the human urinary bladder detrusor tissue. Direct sequencing of the PCR product of the above β3-adrenoceptor revealed no mutation in the amplified regions. In situ hybridization with digoxygenin-labeled oligonucleotide probe revealed the presence of the mRNA of β3-adrenoceptor subtype in the smooth muscle of the urinary bladder. The relaxant effects of isoproterenol (a nonselective β-adrenoceptor agonist); ZD7114, BRL37344, and CGP12177A (putative selective β3-adrenoceptor agonists); and SR59230A (a putative selective β3-adrenoceptor antagonist) were tested using an isometric contraction technique. Isoproterenol in either the presence or absence of both atenolol (a β1-adrenoceptor-selective antagonist) and butoxamine (a β2-adrenoceptor-selective antagonist) revealed a relaxant effect on the carbachol-induced contraction of the human urinary bladder detrusor. Both BRL37344 and CGP12177A also revealed relaxant effects on the human urinary bladder detrusor, but ZD7114 did not elicit any relaxation. These results suggest that β3-adrenoceptor may have some role in urine storage in the human urinary bladder.

Footnotes

  • Send reprint requests to: Masasyuki Takeda, M.D., Department of Urology, Niigata University School of Medicine, Asahimachi 1, Niigata 951-8510, Japan. E-mail:takedama{at}med.niigata-u.ac.jp

  • ↵1 This work was supported by Ministry of Education, Science, and Culture of Japan Grants-in-Aid for Scientific Research 09470342 and 09877312 (M.T.), 09671613 (A.H.), and 09771206 and 10557141 (T.T.). This work also was supported by a grant-in-aid for scientific research from The Japan Spina Bifida and Hydrocephalus Research Foundation (M.T.).

  • Abbreviations:
    RT
    reverse transcription
    PCR
    polymerase chain reaction
    ISH
    in situ hybridization
    IA
    intrinsic activity
    ZD7114
    (S)-4-[2-hydroxy-3-phenoxy-propylamon-ethoxy]-N-(2-methoxyethyl)-phenoxyacetamide
    BRL37344
    (RR +SS)-(±)-4-[2-(2-(3-chlorophenyl)-2-hydroxyethyl)amino)propyl]phenoxyacetate
    CGP12177A
    (±)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one
    SR59230A
    3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronaphth-l-ylamino]2S-2-propanol oxalate
    • Received April 17, 1998.
    • Accepted October 23, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 3
1 Mar 1999
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Research ArticleArticle

Evidence for β3-Adrenoceptor Subtypes in Relaxation of the Human Urinary Bladder Detrusor: Analysis by Molecular Biological and Pharmacological Methods

Masayuki Takeda, Kenji Obara, Takaki Mizusawa, Yoshihiko Tomita, Kei Arai, Toshiki Tsutsui, Akihiko Hatano, Kota Takahashi and Shintaro Nomura
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1367-1373;

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Research ArticleArticle

Evidence for β3-Adrenoceptor Subtypes in Relaxation of the Human Urinary Bladder Detrusor: Analysis by Molecular Biological and Pharmacological Methods

Masayuki Takeda, Kenji Obara, Takaki Mizusawa, Yoshihiko Tomita, Kei Arai, Toshiki Tsutsui, Akihiko Hatano, Kota Takahashi and Shintaro Nomura
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1367-1373;
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