Expression of E-series prostaglandin (EP) receptors and urodynamic effects of an EP₄ receptor antagonist on cyclophosphamide-induced overactive bladder in rats

OBJECTIVE To investigate the expression of four subtypes of E-series prostaglandin (EP₁-EP₄) receptors and the urodynamic effects of an EP₄ receptor antagonist (AH23848) in cyclophosphamide (CYP)-induced overactive bladder (OAB) in rats, as intravesical prostaglandin E₂ (PGE₂) induces OAB via activation of EP receptors and sensitization of afferent nerves. MATERIALS AND METHODS Experimental and control rats were injected with CYP (200 mg/kg, intraperitoneally) or saline, respectively. Continuous cystometrograms (CMGs) were performed 48 h after CYP or saline injection under urethane anaesthesia. AH23848 was given intravenously at doses of 0.01 and 0.1 mg/kg. The bladder was then harvested for histology. Some bladders were harvested for analysis of EP receptors expression by Western blotting without a CMG study. CMG variables (baseline pressure; intercontraction interval [ICI], pressure threshold [PT], contraction amplitude) and histological changes were measured. RESULTS CYP-induced up-regulation of EP ₄ receptor (100% increase) accompanied by detrusor overactivity (ICI 70.5% decrease; PT, 67.7% increase). However, CYP down-regulated EP₁ receptor expression (51.9% decrease), but had no significant effects on the EP₂ and EP₃ receptors. AH23848 significantly extended the ICI in CYP-treated rats but it had no effects on other urodynamic variables or in control rats. CONCLUSIONS Modulation of EP receptors plays a role in CYP-induced OAB. Antagonists to the EP₄ receptor may be a new target for treatment of patients with OAB.