MP17-01 ACID-SENSING ION CHANNELS ARE INVOLVED IN AFFERENT EXCITATORY TRANSMISSION CONTROLLING REFLEX BLADDER ACTIVITY IN MICE

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology1 Apr 2014MP17-01 ACID-SENSING ION CHANNELS ARE INVOLVED IN AFFERENT EXCITATORY TRANSMISSION CONTROLLING REFLEX BLADDER ACTIVITY IN MICE Mitsuharu Yoshiyama, Hideki Kobayashi, Isao Araki, and Masayuki Takeda Mitsuharu YoshiyamaMitsuharu Yoshiyama More articles by this author , Hideki KobayashiHideki Kobayashi More articles by this author , Isao ArakiIsao Araki More articles by this author , and Masayuki TakedaMasayuki Takeda More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.522AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Acid-sensing ion channels (ASICs) have been proposed as transducers of sensory stimuli. ASIC subunits mRNAs are largely expressed in the central nervous systems (CNS), the peripheral nervous system including dorsal root ganglia (DRG) that innervate the bladder, and the bladder (both mucosa and detrusor), suggesting the possibility that ASICs are involved in regulation of lower urinary tract (LUT) activity. In this study, we examined effects of A-317567, a non-amiloride blocker of ASICs, on activity of LUT with or without acid irritation. METHODS C57BL/6 female mice (12-13 week-old) were anesthetized with sevoflurane during surgery including precollicular decerebration. A PE-50 tube was inserted into the bladder dome to record intravesical pressure. Cystometrogram (CMG) recordings under unanesthetized conditions were performed by continuously infusing (30 μl/min) saline alone or saline followed by dilute acetic acid (A/A, pH 3). CMG parameters were: pressure threshold for inducing micturition (PT); maximal voiding pressure (MVP), bladder compliance (BCP), bladder contraction duration (BCD), and inter-contraction interval (ICI). A-317567 was infused intravesically (100 μM) or injected i.p. (30 mg/kg), and effects of the drug were compared with those of the vehicle. All values are expressed as mean ± S.E.M. For statistical analysis, two-way repeated measures ANOVA and Wilcoxon matched-pairs signed rank test were used, and P ≤ 0.05 was considered significant. RESULTS I.p. administration of A-317567 increased PT and ICI and decreased BCP during saline infusion CMG, whereas it produced no changes in MVP and BCD (Fig. 1A). The i.p. dose ameliorated bladder hyperactivity (i.e., exhibited as decreased ICI) induced by intravesical A/A perfusion (Fig. 1B). However, intravesical infusion of the drug had no effects on activity of the LUT either with or without acid irritation. Neither intravesical infusion nor i.p. injection of the vehicle produced significant effects on both normal LUT activity and A/A-induced bladder hyperactivity. CONCLUSIONS ASICs participate in afferent excitatory transmission controlling reflex bladder activity under conditions of the LUT either with or without acid irritation. ASICs in the DRG, the CNS or both, but not in the bladder, play the essential role. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e135-e136 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Mitsuharu Yoshiyama More articles by this author Hideki Kobayashi More articles by this author Isao Araki More articles by this author Masayuki Takeda More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...