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Further characterization of a novel EP2 and EP3 receptor dual agonist, ONO‐8055, on lower urinary tract function in normal and lumbar canal stenosis rats
Author(s) -
Sekido Noritoshi,
Kida Jun,
Otsuki Takeya,
Mashimo Hiroko,
Matsuya Hidekazu,
Okada Hiroki
Publication year - 2020
Publication title -
luts: lower urinary tract symptoms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.451
H-Index - 15
eISSN - 1757-5672
pISSN - 1757-5664
DOI - 10.1111/luts.12284
Subject(s) - cystometry , agonist , endocrinology , medicine , receptor , urinary system , urinary bladder , contractility , lumbar , ureter , urology , anatomy
Aims To further explore the effects of a novel EP2 and EP3 dual agonist, ONO‐8055, on detrusor contractility, we investigated the responses of bladder strips from sham and lumbar canal stenosis (LCS) rats to this agonist, its effects on lower urinary tract function in normal rats, and mRNA expression of EP2 and EP3 receptors in the sham and LCS rats. Methods The responses of bladder strips from sham and LCS rats to ONO‐8055 were measured. The effects of ONO‐8055 on LUT function of normal rats were investigated with awake cystometry and intraurethral perfusion pressure (Pura) measurements. The relative mRNA of bladder and urethral tissue of the sham and LCS rats was quantified using specific probes for EP1 , EP2 , EP3 , and EP4 genes. Results Compared with the vehicle, the muscle tensions of both the sham and LCS rats were significantly increased after adding this agonist. On awake cystometry of normal rats, bladder capacity and Pura were decreased in the ONO‐8055 groups, but a statistically significant difference in mean changes was demonstrated only between the vehicle group and the group receiving the highest dose. Compared with the sham rats, mRNA expressions of the four EP receptors in the lower urinary tract of the LCS rats did not show a statistically significant difference. Conclusions This agonist did not augment bladder contractility or urethral relaxation in normal rats.