Abstract | OBJECTIVES: To evaluate, using a rat model of non-bacterial prostatic inflammation, the prostaglandin production and expression profiles of E-series prostaglandin (EP) receptor subtypes, which are reportedly implicated in the development of overactive bladder, in the bladder mucosa, and to investigate the effect of EP receptor type 4 (EP4) blockade on bladder overactivity after prostatic inflammation. METHODS: Male Sprague-Dawley rats were used. Prostatic inflammation was induced by formalin injection (5%; 50 μL per lobe) into the bilateral ventral lobes of the prostate. At 10 days after induction of prostatic inflammation or vehicle injection, bladder tissues from the deeply anaesthetized rats were harvested and separated into mucosal and detrusor layers. Then, prostaglandin E2 ( PGE2) concentrations and protein levels of PGE2 receptors (EP1-4) in the bladder mucosa and detrusor were measured by ELISA and Western blotting, respectively. In separate groups of control and formalin-treated rats, awake cystometry was performed to evaluate the changes in bladder activity after prostatic inflammation. In addition, the effect of intravesical administration of a selective EP4 antagonist (ONO- AE3-208; 30 μm) on bladder activity was evaluated in control rats and rats with prostatic inflammation. RESULTS:
PGE2 concentration and protein levels of EP4, but not other EP receptor subtypes, in the bladder mucosa and detrusor layers were significantly increased in formalin-injected rats vs vehicle-injected control rats. In cystometry, rats with prostatic inflammation exhibited a significant decrease in intercontraction intervals (ICIs) compared with control rats. Intravesical application of ONO-AE3-208 (30 μm), but not vehicle application, significantly increased ICIs in rats with prostatic inflammation, whereas ONO-AE3-208 at this concentration did not significantly affect any cystometric values in control rats. CONCLUSIONS:
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Authors | Shinsuke Mizoguchi, Amanda S Wolf-Johnson, Jianshu Ni, Kenichi Mori, Takahisa Suzuki, Eiichiro Takaoka, Hiromitsu Mimata, Donald B DeFranco, Zhou Wang, Lori A Birder, Naoki Yoshimura |
Journal | BJU international
(BJU Int)
Vol. 124
Issue 5
Pg. 883-891
(11 2019)
ISSN: 1464-410X [Electronic] England |
PMID | 31166645
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd. |
Chemical References |
- Prostaglandins E
- Receptors, Prostaglandin E
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Topics |
- Animals
- Disease Models, Animal
- Inflammation
(metabolism, physiopathology)
- Male
- Mucous Membrane
(metabolism)
- Prostaglandins E
(metabolism)
- Prostatitis
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptors, Prostaglandin E
(antagonists & inhibitors, metabolism)
- Urinary Bladder
(metabolism, physiopathology)
- Urinary Bladder, Overactive
(metabolism, physiopathology)
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