Bladder outlet obstruction induced expression of prostaglandin E2 receptor subtype EP4 in the rat bladder: a possible counteractive mechanism against detrusor overactivity.
OBJECTIVE
Prostaglandins have been implicated as endogenous modulators of bladder function under physiological and pathological conditions. We examined how the expression of each EP receptor subtype changed in association with bladder outlet obstruction and focused on the functional role of EP4 receptor subtype in the bladder with outlet obstruction.


METHODS
We assessed the gene expression of EP receptor subtypes by reverse transcriptase-polymerase chain reaction. EP4 protein localization was determined by immunohistochemistry. The effect of the selective EP4 agonist ONO-AE1-329 on 50 mM KCl induced contraction of rat bladder strips was examined in vitro. Continuous infusion cystometrograms were done to examine the effect of intravesical perfusion of ONO-AE1-329 on the micturition reflex in urethane anesthetized rats.


RESULTS
EP4 receptor genes were largely expressed in bladders with outlet obstruction but absent in controls. EP4 receptor proteins were clearly detected in obstructed bladder detrusor smooth muscle and epithelium. ONO-AE1-329 (100 μM) significantly relaxed KCl induced contraction of bladder strips from rats with bladder outlet obstruction. A significant correlation was found between the relaxant effect of ONO-AE1-329 and whole bladder weight. In rats with bladder outlet obstruction intravesical infusion of 10 μM ONO-AE1-329 significantly increased bladder capacity without changing micturition pressure while it had no effect in controls.


CONCLUSIONS
Activation of the EP4 receptors expressed in bladders with outlet obstruction may suppress detrusor muscle contraction and afferent activity. This might be a compensatory mechanism to counteract the deterioration of storage function in bladders with outlet obstruction.
Department of Urology, University of Yamanashi and Interdisciplinary Graduate School of Medicine and Engineering, Yamanashi, Japan.
Masanori
M
Beppu
Isao
I
Araki
Mitsuharu
M
Yoshiyama
Shuqi
S
Du
Hideki
H
Kobayashi
Hidenori
H
Zakoji
Masayuki
M
Takeda
D000818:Animals; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000096:biosynthesis* / Q000502:physiology; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism*; D053201:Urinary Bladder, Overactive / Q000378:metabolism*
D058309:Receptors, Prostaglandin E, EP4 Subtype