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EP2 and EP3 receptors as therapeutic targets for underactive bladder/detrusor underactivity due to diabetic cystopathy in a type 1 diabetic rat model
Author(s) -
Sekido Noritoshi,
Otsuki Takeya,
Kida Jun,
Mashimo Hiroko,
Wakamatsu Daisuke,
Okada Hiroki,
Matsuya Hidekazu
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.12317
Subject(s) - medicine , urology , receptor
Objectives Diabetic cystopathy (DC) is recognized as one of the major etiologies of underactive bladder (UAB)/detrusor underactivity (DU). Although DC was first reported about three decades ago, there is a distinct lack of effective pharmacological management methods for UAB/DU due to DC with a robust certainty of evidence. In this study, we investigated whether EP2 and EP3 receptors are promising targets of pharmacological management of UAB/DU due to DC. Methods We used streptozotocin (STZ)‐induced diabetic Sprague‐Dawley rats with postvoid residual urine (PVR) greater than 0.1 mL. Sixteen weeks after induction of diabetes, we performed awake single cystometry after oral administration of the vehicle, an α‐blocker (tamsulosin [TAM], 0.1 and 0.3 mg/kg), a cholinesterase inhibitor (distigmine [DIS], 0.3 and 1.0 mg/kg), or an EP2/3 dual agonist (ONO‐8055, 0.01 and 0.03 mg/kg). We compared cystometric parameters after administration of the vehicle and drugs using a paired t test. P < .05 was considered to be statistically significant. Results Compared with the vehicle, TAM significantly decreased maximum intravesical pressure during voiding (Pmax), while DIS significantly increased it. However, neither drug significantly affected PVR or the residual urine rate (RUR). On the other hand, ONO‐8055 significantly decreased PVR and tended to decrease RUR, although it did not significantly affect Pmax. Conclusion The present study was unable to demonstrate that stimulation of EP2 and EP3 receptors caused major improvements in UAB/DU due to DC. However, this equivocal result could arise from inherent limitations of the STZ‐induced diabetic rat as a UAB/DU model.