Therapeutic Effects of Prostaglandin E2 Receptor Subtype 3 Blockade on Spinal Cord Injury-Induced Detrusor Overactivity

Objective: Detrusor overactivity (DO) is a severe urological disorder in spinal cord injury (SCI) patients. Conventional pharmacological interventions, such as antimuscarinic agents, show limited therapeutic efficacy and are often associated with adverse effects. Emerging evidence indicates that prostaglandin E2 (PGE2) and its E-prostanoid 3 (EP3) receptor play a pivotal regulatory role in bladder function. This study aimed to investigate whether EP3 receptor antagonism can alleviate DO after SCI.

Methods: Bladder PGE2 and cyclooxygenase-2 levels were assessed after SCI. Urodynamic alterations were evaluated by cystometry. The EP3 receptor antagonist L- 826266 (0.1 or 1.0 mg/kg) was intravenously administered to SCI rats. Urodynamic parameters, bladder cyclic adenosine monophosphate levels, histopathological changes, and preliminary systemic safety parameters were further assessed. L-826266 was also tested in PGE2-induced and acetic acid-induced overactive bladder (OAB) models and in healthy rats.

Results: SCI increased bladder PGE2 and cyclooxygenase-2 levels and induced nonvoiding contractions (NVCs) during bladder storage phase. Both doses of L-826266 (0.1 and 1.0 mg/kg) increased the intercontraction interval, bladder capacity, and voiding efficiency and reduced NVC frequency in SCI rats. L-826266 also increased bladder cyclic adenosine monophosphate levels without obvious systemic toxicity or histopathological aggravation. In PGE2-induced OAB rats, L-826266 increased bladder capacity and reduced NVC frequency, whereas it had minimal effects on acetic acidinduced OAB. In healthy rats, only 1.0 mg/kg L-826266 prolonged the intercontraction interval and increased bladder capacity.

Conclusion: EP3 receptor antagonist significantly reduced DO in SCI rats, which provides novel insights into the therapeutic agents for bladder dysfunction after SCI.

Cite this article as: Lv LC, Xu XJ, Guo DY, et al. Therapeutic effects of prostaglandin E2 receptor subtype 3 blockade on spinal cord injury-induced detrusor overactivity. Urol Res Pract. 2026;52, doi:10.5152/tud.2026.26041