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Expression and functional role of β-adrenoceptors in the human urinary bladder urothelium

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Abstract

We investigated the presence of β-adrenoceptor subtypes in human urinary bladder urothelium and examined whether β-adrenoceptors in the urothelium modulate the relaxation responses of isolated human detrusor strips to a β-adrenoceptor agonist. Expression of β1-, β2-, and β3-adrenoceptor mRNA in urothelium and detrusor smooth muscle was determined by reverse transcription-polymerase chain reaction, and the distribution of β1-, β2-, and β3-adrenoceptors in human urinary bladder urothelium were examined by immunohistochemistry. Paired human longitudinal detrusor strips with and without an intact urothelium were suspended in organ baths to construct concentration-response curves to isoproterenol. The possible involvement of urothelium-derived nitric oxide (NO) in this response was examined in additional experiments with urothelium-intact strips in the presence of N G-nitro-L-arginine methylester (L-NAME). Results confirmed the expression of β1-, β2-, and β3-adrenoceptors in the human urinary bladder urothelium. Further, the presence of the urothelium caused a parallel rightward shift of the concentration-response curve to isoproterenol with a significant reduction in potency (pEC50). L-NAME failed to exert any significant effect on the relaxation response to isoproterenol in the urothelium-intact strips. These results confirm the presence of β1-, β2-, and β3-adrenoceptors in human urinary bladder urothelium. Further, they suggest that urothelial β-adrenoceptors induce the release of a urothelium-derived factor which inhibits the β-adrenoceptor agonist-induced relaxation of the human detrusor smooth muscle and that this inhibitory mechanism might not involve NO.

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Abbreviations

RT–PCR:

reverse transcription-polymerase chain reaction

L-NAME:

N G-nitro-L-arginine methyl ester

NO:

nitric oxide

pEC50 :

potency, negative logarithm of the concentration giving half-maximal effect

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Acknowledgements

We wish to thank Drs. K Hasebe and H Kawasaki for their technical advice and Ms. T Kageyama for her technical assistance. We also express our gratitude to members of the affiliated hospitals of the Department of Urology, Hamamatsu University School of Medicine: Dr. H Terada, Dr. S Kageyama, Dr. T Nakanishi, and Dr. T Mizuno.

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Authors and Affiliations

  1. Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan

    Atsushi Otsuka, Hitoshi Shinbo, Rikiya Matsumoto, Yutaka Kurita & Seiichiro Ozono

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  1. Atsushi Otsuka
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  2. Hitoshi Shinbo
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  3. Rikiya Matsumoto
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  4. Yutaka Kurita
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  5. Seiichiro Ozono
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Correspondence to Atsushi Otsuka.

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Otsuka, A., Shinbo, H., Matsumoto, R. et al. Expression and functional role of β-adrenoceptors in the human urinary bladder urothelium. Naunyn-Schmied Arch Pharmacol 377, 473–481 (2008). https://doi.org/10.1007/s00210-008-0274-y

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  • DOI: https://doi.org/10.1007/s00210-008-0274-y

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