MP82-09 ENHANCEMENT OF SNEEZE-INDUCED URETHRAL CONTINENCE REFLEX VIA SEROTONIN TYPE 7 RECEPTORS IN RATS

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II1 Apr 2017MP82-09 ENHANCEMENT OF SNEEZE-INDUCED URETHRAL CONTINENCE REFLEX VIA SEROTONIN TYPE 7 RECEPTORS IN RATS Takahisa Suzuki, Takahiro Shimizu, Joombeom Kwon, Eiichiro Takaoka, Shun Takai, Nobutaka Shimizu, Naoki Wada, Seiichiro Ozono, and Naoki Yoshimura Takahisa SuzukiTakahisa Suzuki More articles by this author , Takahiro ShimizuTakahiro Shimizu More articles by this author , Joombeom KwonJoombeom Kwon More articles by this author , Eiichiro TakaokaEiichiro Takaoka More articles by this author , Shun TakaiShun Takai More articles by this author , Nobutaka ShimizuNobutaka Shimizu More articles by this author , Naoki WadaNaoki Wada More articles by this author , Seiichiro OzonoSeiichiro Ozono More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2556AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The spinal serotonin (5HT) system is well known to be involved in the control of lower urinary tract function, and we previously reported that 5HT receptors such as 5HT1A or 5HT2C, have respectively inhibit or enhance the urethral continence reflex during sneezing in rats. However, because there are multiple 5HT receptor subtypes, it is often difficult to determine the subtype-specific mechanism. Thus, we examined the role of 5HT7 receptors in the urethral continence mechanism using a rat model of stress urinary incontinence (SUI), in which endogenous 5HT was depleted by p-chlorophenylalanine (PCPA). METHODS Female Sprague-Dawley rats were used. PCPA (200 mg/kg/day) was administered intraperitoneally for two days. Thereafter, using a microtransducer-tipped catheter inserted to the mid-urethra, we assessed urethral baseline pressure (UBP), amplitudes of urethral responses during sneezing (AURS) and abdominal pressure during sneezing (Pabd) under urethane anesthesia before and after administration of following drugs. First, we investigated the effects of a 5HT7 and partial 5HT1A agonist (LP 44 = LP, 0.3mg/kg, iv) in PCPA-administered rats. To suppress the partial 5HT1A effect of LP, a 5HT1A antagonist (WAY 100635 = WAY, 0.1 mg/kg, iv) was administered before LP treatment. Secondly, we investigated whether the effects of LP in the presence of WAY were inhibited by a 5HT7 antagonist (SB 269970 = SB, 0.1 mg/kg, iv), which was administered with WAY prior to LP administration. All data are shown in cmH2O. RESULTS After LP administration (n = 6), UBP and AURS were significantly increased compared to the PCPA + WAY (n = 4) or PCPA only group (n = 7) (UBP: 15.2 vs 16.8 vs 26.6, AURS: 30.0 vs 32.2 vs 50.5 [PCPA only vs PCPA + WAY vs PCPA + WAY + LP], respectively) (Figure). However, in the presence of the SB, UBP and AURS were not significantly increased after LP administration (n = 6) compared to the PCPA + WAY (n = 6) or PCPA only group (n = 6). Pabd had no statistical difference among groups. CONCLUSIONS The 5HT7 receptor exerts the facilitatory effects on the urethral baseline activity and the urethral continence reflex during stress conditions such as sneezing, which are reportedly attributable to contractions of smooth and striated urethral sphincter muscles, respectively. Thus, 5HT7 agonists could be effective for the treatment of SUI. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1100 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Takahisa Suzuki More articles by this author Takahiro Shimizu More articles by this author Joombeom Kwon More articles by this author Eiichiro Takaoka More articles by this author Shun Takai More articles by this author Nobutaka Shimizu More articles by this author Naoki Wada More articles by this author Seiichiro Ozono More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...