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Effects of 138–355, a β 3 ‐adrenoceptor selective agonist, on relaxation of the human detrusor muscle in vitro
Author(s) -
Yamanishi Tomonori,
Yasuda Kosaku,
Kitahara Satoshi,
Nakai Hideo,
Yoshida KenIchiro,
Iizuka Hiroyuki
Publication year - 2006
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20231
Subject(s) - medicine , agonist , detrusor muscle , relaxation (psychology) , urology , in vitro , overactive bladder , muscle relaxation , pharmacology , receptor , endocrinology , urinary bladder , pathology , chemistry , biochemistry , alternative medicine
Aims β‐adrenoceptors are the predominant β‐adrenoceptor subtype present in the bladder and urethra. This study investigates the effects of 138–355, an active‐metabolite of TT‐138 and β 3 ‐adrenoceptor agonist, on relaxation of the human detrusor in vitro. Methods Tumor‐free tissue samples of human bladder muscle from 39 patients undergoing total cystectomy due to bladder cancer were obtained, and the mucosa and serosa were removed. Tissues were mounted in 5 or 10 ml organ baths containing Krebs solution, which was gassed with 95% O 2 and 5% CO 2 . Resting tension of 1 g was obtained. When the contraction had stabilized, increasing concentrations of β adrenoceptor agonists (non‐selective, isoprenaline; β 2 ‐selective, clenbuterol; β 3 ‐selective, 138–355 and BRL37344) and propiverine (a non‐selective anti‐muscarinic antagonist) were added cumulatively and concentration‐relaxation curves (CRCs) were obtained. CRCs to 138–355 were obtained in the absence and presence of SR59230A, a β 3 ‐selective antagonist, and antagonist affinity values (pA 2 ) were calculated from the Schild plot. Results Isoproterenol, clenbuterol, 138–355 and BRL37344 concentration‐dependently relaxed isolated human urinary bladder strips with pEC 50 value being 6.76±0.17, 5.23±0.22, 5.80±0.26 and 5.90±0.28, respectively. Following antagonist assay, it was observed that concentration‐relaxation curves to 138–355 was competitively antagonized by β 3 ‐ adrenoceptor antagonist, SR59230A, with a pA 2 value of 7.01±0.45 and with a Schild slope of 0.72±0.07. Conclusions Involvement of the β 3 ‐adrenoceptor appears to be greater than that of the β 3 ‐adrenoceptor for relaxations of the human bladder. The relaxation response of 138–355 appears to be mediated via the β 3 ‐adrenoceptor stimulation. Neurourol. Urodynam. 25:815–819, 2006. © 2006 Wiley‐Liss, Inc.