Bladder Outlet Obstruction Induced Expression of Prostaglandin E ₂ Receptor Subtype EP4 in the Rat Bladder: A Possible Counteractive Mechanism Against Detrusor Overactivity

Abstract

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.

Bladder overactivity and afferent hyperexcitability induced by prostate‐to‐bladder cross‐sensitization in rats with prostatic inflammation

“…Lower urinary tract symptoms (LUTS) are commonly seen in males with benign prostatic hyperplasia (BPH), and storage LUTS such as urinary frequency and urgency overlap with those of overactive bladder. BPH-induced bladder outlet obstruction (BOO) has been proposed as a mechanism inducing enhanced bladder afferent activity and storage LUTS due to various factors including decreased release of nitric oxide (Kim et al 2011), increased release of prostaglandin E2 from the urothelium (Beppu et al 2011), decreased potassium channel activity (Aydin et al 2012), or ischaemia and oxidative stress to the detrusor (Lin et al 2008). However, the size of prostate and LUTS severity do not always correlate and patients sometimes suffer LUTS even in the absence of prostate enlargement, which suggests that multiple factors contribute to the pathogenesis of LUTS (Funahashi et al 2011;Chung et al 2012).…”

High luteinizing hormone weakens urinary continence mechanisms in association with prostaglandin E2 elevation in a postmenopausal rat model

“…It has been reported that LH binds to the LH receptor and activates the cyclic adenosine monophosphate/protein kinase A pathway and the phospholipase/inositol phosphate signaling pathways in human uterine smooth muscle cell . These pathways increase cyclooxygenase and the production of PGE2, which induces relaxation of the urethra in the lower urinary tract in humans, suggesting that increasing the PGE2 concentration could lead to urinary incontinence. In the rat urethra, PGE2 is thought to relax smooth muscle and decrease urethral pressure .…”

Effect of Selective Prostaglandin E2 EP2 Receptor Agonist CP‐533,536 on Voiding Efficiency in Rats with Midodrine‐Induced Functional Urethral Obstruction

“…Previous studies have shown that the excitatory effect of PGE 2 on bladder function is inhibited by an EP1 antagonist in rats and is suppressed in EP3 receptor knockout mice . Concerning the role of EP4 receptor, one study reported that an EP4 receptor antagonist attenuated bladder activity in rats with overactive bladder induced by cyclophosphamide, whereas another reported that an EP4 receptor agonist suppressed bladder activity in rats with bladder outlet obstruction . Further studies are required to elucidate the mechanisms underlying EP4 receptor signaling.…”

“…20 Concerning the role of EP4 receptor, one study reported that an EP4 receptor antagonist attenuated bladder activity in rats with overactive bladder induced by cyclophosphamide, 21 whereas another reported that an EP4 receptor agonist suppressed bladder activity in rats with bladder outlet obstruction. 22 Further studies are required to elucidate the mechanisms underlying EP4 receptor signaling. Regarding involvement of EP2 receptor in the bladder, a couple of reports have suggested that EP2 receptors might be expressed in guinea pig bladders.…”