537 INHIBITION OF THE ANANDAMIDE TRANSPORTER INHIBITS THE MICTURITION REFLEX OF ANESTHETIZED RATS (2013)

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology (II)1 Apr 2013537 INHIBITION OF THE ANANDAMIDE TRANSPORTER INHIBITS THE MICTURITION REFLEX OF ANESTHETIZED RATS Masashi Honda, Seiya Inoue, Katsuya Hikita, Kuniyasu Muraoka, Motoaki Saito, Takehiro Sejima, Atsushi Takenaka, Michael Chancellor, and Naoki Yoshimura Masashi HondaMasashi Honda Yonago, Japan More articles by this author , Seiya InoueSeiya Inoue Yonago, Japan More articles by this author , Katsuya HikitaKatsuya Hikita Yonago, Japan More articles by this author , Kuniyasu MuraokaKuniyasu Muraoka Yonago, Japan More articles by this author , Motoaki SaitoMotoaki Saito Yonago, Japan More articles by this author , Takehiro SejimaTakehiro Sejima Yonago, Japan More articles by this author , Atsushi TakenakaAtsushi Takenaka Yonago, Japan More articles by this author , Michael ChancellorMichael Chancellor Royal Oak, MI More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1932AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Anandamide is an endogenous cannabinoid (CB) receptor ligand. Recent studies have also demonstrated that anandamide plays an important role in the modulation of micturition reflex. However, it is unknown whether the anandamide transporters play a role in this modulation. In the current study we tested whether N-arachidonoyl-(2-methyl-4-hydroxyphenyl) amine (VDM11), an anandamide transporter inhibitor that increases endogenous anandamide concentration, can affect the micturition reflex in rats. METHODS Female Sprague-Dawley rats (247-261 g) were used. Continuous cystometrograms (CMG, 0.04ml/min) were performed in urethane-anesthetized rats. After stable micturition cycles were established, VDM11 (1, 3 and 10 mg/kg, n=6 per dose) was injected intravenously to evaluate changes in bladder activity. In experiments examining the effects of CB receptor antagonists, VDM11 (10 mg/kg) was injected intravenously when the first bladder contraction was observed after intravenous administration of AM251, a CB1 antagonist (3 mg/kg, n=6), or AM630, a CB2 antagonist (3 mg/kg, n=6). Micturition parameters were recorded and compared before and after drug administration. RESULTS Intravenous administration of VDM11 at 1, 3 and 10 mg/kg increased intercontraction intervals at doses of 3 mg/kg or higher in dose dependent fashion to 103.3 ± 2.3%, 117.2 ± 3.6% and 144.5 ± 10.6% of the control value, respectively (at 3 and 10 mg/kg, p<0.01). Intravenous administration of VDM11 at 1, 3 and 10 mg/kg also increased threshold pressure at doses of 3 mg/kg or higher in dose dependent fashion. There were no significant changes in basal pressure or maximum pressure at any doses tested. When AM251 was administered one voiding cycle before VDM11 administration, the increases in intercontraction intervals and threshold pressure induced by VDM11 administration alone were not seen. In contrast, when AM630 was administered before VDM11 administration, increases in intercontraction intervals and threshold pressure were still observed, as they were after VDM11 alone. CONCLUSIONS These results suggest that anandamide transporters play an important role in the modulation of micturition reflex. Furthermore, these findings indicate that, in urethane-anesthetized rats, inhibition of the uptake of anandamide by VDM11 can inhibit the micturition reflex at least in part via activation of the CB1 receptor, but not the CB2 receptor. Thus, anandamide transporter inhibitors could be effective for the treatment of bladder dysfunction such as overactive bladder. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e220-e221 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masashi Honda Yonago, Japan More articles by this author Seiya Inoue Yonago, Japan More articles by this author Katsuya Hikita Yonago, Japan More articles by this author Kuniyasu Muraoka Yonago, Japan More articles by this author Motoaki Saito Yonago, Japan More articles by this author Takehiro Sejima Yonago, Japan More articles by this author Atsushi Takenaka Yonago, Japan More articles by this author Michael Chancellor Royal Oak, MI More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...