Takaoka, E., Kurobe, M., Matsuoka, K. et al. (5 more authors) (2025) Adenosine receptor mechanisms underlying bladder dysfunction in male rats with bladder outlet obstruction. Neurourology and Urodynamics. ISSN 0733-2467
Abstract
Aims
We examined the role of subtypes of adenosine receptors in bladder dysfunction and changes in the adenosine receptor expression in the bladder using male rats with partial bladder outlet obstruction (BOO).
Methods
In Sprague-Dawley rats (male 8-weeks old), BOO was produced by a partial ligation of the urethra along a metal rod of a 1.2 mm outer diameter. Control rats underwent sham operation. Awake cystometrograms (CMG) were first recorded during saline instillation, and then an adenosine A1 receptor agonist (CCPA, 4.1 μM), an adenosine A2A antagonist (ZM241385, 15 μM), or inosine (1 mM) were applied intravesically in sham and BOO rats. In addition, mRNA levels of adenosine receptor subtypes in the bladder wall were measured using RT-PCR. Histological studies of bladder specimen were also performed.
Results
Weights of BOO bladders were significantly (p < 0.0001) larger compared with sham bladders. In CMG, a number of non-voiding contractions (NVCs), bladder contraction amplitudes during voiding, bladder capacity, and post-void residual (PVR) were significantly (p < 0.001) increased compared with sham rats. Voiding efficiency (VE) was significantly (p < 0.001) reduced in BOO versus sham rats. Intravesical application of CCPA or inosine did not induce statistically significant effects on CMG parameters in BOO rats. Yet, ZM241385 induced a significant (p = 0.040) reduction in NVCs of BOO rats. mRNA levels of adenosine A2A and A3 receptors were significantly (p < 0.0001 and p = 0.0145, respectively) upregulated in the BOO bladder mucosa, whereas adenosine A2B receptors showed a significant (p < 0.0001) reduction in the BOO bladder mucosa compared with sham bladders. Histologically, we found the thickened detrusor muscle layer in BOO versus sham rats.
Conclusions
The male rat model of BOO seems to be suitable for exploring urethral obstruction-related bladder dysfunction at the compensated phase. In addition, the adenosine A2A receptor subtype would be a potential target for the treatment of male BOO patients with bladder overactivity.
Clinical Trial Registration
A clinical trial registration is not required as this study reported the basic research data using animal models.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Computer Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 28 May 2025 10:30 |
Last Modified: | 28 May 2025 10:30 |
Status: | Published online |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/nau.70080 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:227132 |