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Vol. 288, Issue 3, 1367-1373, March 1999

Evidence for beta 3-Adrenoceptor Subtypes in Relaxation of the Human Urinary Bladder Detrusor: Analysis by Molecular Biological and Pharmacological Methods1

Masayuki Takeda, Kenji Obara, Takaki Mizusawa, Yoshihiko Tomita, Kei Arai, Toshiki Tsutsui, Akihiko Hatano, Kota Takahashi and Shintaro Nomura

Department of Urology, Niigata University School of Medicine, Niigata, Japan (M.T., K.O., T.M., Y.T., K.A., T.T., A.H., K.T.); and Department of Pathology, Osaka University School of Medicine, Osaka, Japan (S.N.).

The purpose of the present study was to confirm the presence of beta 3-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 (beta 1, beta 2, and beta 3) were expressed in the human urinary bladder detrusor tissue. Direct sequencing of the PCR product of the above beta 3-adrenoceptor revealed no mutation in the amplified regions. In situ hybridization with digoxygenin-labeled oligonucleotide probe revealed the presence of the mRNA of beta 3-adrenoceptor subtype in the smooth muscle of the urinary bladder. The relaxant effects of isoproterenol (a nonselective beta -adrenoceptor agonist); ZD7114, BRL37344, and CGP12177A (putative selective beta 3-adrenoceptor agonists); and SR59230A (a putative selective beta 3-adrenoceptor antagonist) were tested using an isometric contraction technique. Isoproterenol in either the presence or absence of both atenolol (a beta 1-adrenoceptor-selective antagonist) and butoxamine (a beta 2-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 beta 3-adrenoceptor may have some role in urine storage in the human urinary bladder.


0022-3565/99/2883-1367$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics



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