J Urol. 2016 Feb 12;

Authors: Sekido N, Kida J, Mashimo H, Wakamatsu D, Okada H, Matsuya H

Abstract
PURPOSE: We investigated whether a novel EP receptor agonist, ONO-8055, improved the lower urinary tract dysfunctions of neurogenic underactive bladder in a rat lumbar spinal canal stenosis (LCS) model.
MATERIALS AND METHODS: First, the agonistic effect of ONO-8055 on EP receptors was studied in EP receptor-expressing Chinese hamster ovary (CHO) cells using the increase in intracellular calcium level and intracellular cAMP production as indicators of receptor activation. Then, the effects of ONO-8055 on bladder and urethral strips from normal rats were investigated. Finally, the effects of ONO-8055 on the bladder and urethral function in LCS rats were evaluated by awake cystometry and intraurethral perfusion pressure, respectively. The effects of tamsulosin and distigmine on urethral pressure were also evaluated.
RESULTS: ONO-8055 is a highly potent and selective agonist for both EP2 and EP3 receptors on CHO cells. While this compound contracted bladder strips, it relaxed urethral strips. Awake cystometry showed that ONO-8055 significantly decreased bladder capacity, residual urine, and voiding pressure. Compared with the vehicle, tamsulosin and ONO-8055 significantly decreased urethral pressure.
CONCLUSIONS: ONO-8055 decreased residual urine, probably through decreasing bladder capacity The decrease in voiding pressure probably resulted from the lowered urethral pressure due to its relaxation of the urethra. Thus, ONO-8055, a novel EP2 and EP3 receptor dual agonist, has potential to improve neurogenic underactive bladder.

PMID: 26880410 [PubMed – as supplied by publisher]