MP94-08 GROUP III METABOTROPIC GLUTAMATE RECEPTOR-MEDIATED REGULATION OF MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II1 Apr 2017MP94-08 GROUP III METABOTROPIC GLUTAMATE RECEPTOR-MEDIATED REGULATION OF MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS Masashi Honda, Yusuke Kimura, Bunya Kawamoto, Panagiota Tsounapi, Katsuya Hikita, Shogo Shimizu, Takahiro Shimizu, Motoaki Saito, and Atsushi Takenaka Masashi HondaMasashi Honda More articles by this author , Yusuke KimuraYusuke Kimura More articles by this author , Bunya KawamotoBunya Kawamoto More articles by this author , Panagiota TsounapiPanagiota Tsounapi More articles by this author , Katsuya HikitaKatsuya Hikita More articles by this author , Shogo ShimizuShogo Shimizu More articles by this author , Takahiro ShimizuTakahiro Shimizu More articles by this author , Motoaki SaitoMotoaki Saito More articles by this author , and Atsushi TakenakaAtsushi Takenaka More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2911AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The modulatory actions of glutamate, the main excitatory neurotransmitter in the central nervous system, are exerted via activation of metabotropic glutamate receptors (mGluRs). Eight distinct mGluRs (mGluR1-8) have been classified into three groups (I-III) based on their sequence homology. Group III mGluRs (mGluRIII; mGluR4, mGluR6, mGluR7 and mGluR8) are widely distributed throughout the central nervous system. However, it is unknown whether mGluRIII plays a role in the regulation of neural mechanisms controlling the micturition reflex. In the present study, we assessed whether L-(+)-2-amino-4-phosphonobutyric acid (L-AP4), a selective mGluRIII agonist, affects the micturition reflex in urethane-anesthetized rats. METHODS Adult female Sprague-Dawley rats weighing 238 to 261 g were used. Continuous cystometrograms (CMG, 0.04 ml/min infusion rate) were performed in two groups of urethane-anesthetized rats. A group of 24 rats was used for intracerebroventricular administration of 1-10 µg of L-AP4 via a catheter inserted into the lateral ventricle. Using a stereotaxic micro-injector, a 30 gauge needle attached to a 10 µl Hamilton syringe was inserted into the lateral ventricle and single doses of drugs were administered in a volume of 2 µl during 2 minutes. In the second group of 24 rats, 1-10 µg of L-AP4 were administered intrathecally via an intrathecal catheter. Intrathecal injections were made through a polyethylene-10 (PE-10) catheter positioned at the level of the L6-S1 spinal cord. A PE-10 intrathecal catheter was implanted using isoflurane anesthesia 3 days before the experiments. Cystometric parameters were recorded and compared before and after drug administration. RESULTS Intracerebroventricular administration of L-AP4 at doses of 1, 3 and 10 μg (n=8 per dose) increased intercontraction intervals in a dose dependent fashion to 117.1 ± 12.3%, 132.5 ± 10.5% and 137.1 ± 15.6% of the control value, respectively (p <0.01), but did not affect residual urine or baseline pressure at any of the doses tested. Intrathecal administration of L-AP4 at doses of 1, 3 and 10 μg (n=8 per dose) also increased intercontraction intervals in a dose dependent fashion to 125.3 ± 8.2%, 136.9 ± 7.1% and 142.7 ± 12.6% of the control value, respectively (p <0.01), but did not affect residual urine or baseline pressure at any of the doses tested. CONCLUSIONS The results of our study indicate that in urethane-anesthetized rats activation of mGluRIII can inhibit the micturition reflex at supraspinal and spinal sites. Thus, mGluRIII could be a potential target for the treatment of bladder dysfunction, such as overactive bladder. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1248 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Masashi Honda More articles by this author Yusuke Kimura More articles by this author Bunya Kawamoto More articles by this author Panagiota Tsounapi More articles by this author Katsuya Hikita More articles by this author Shogo Shimizu More articles by this author Takahiro Shimizu More articles by this author Motoaki Saito More articles by this author Atsushi Takenaka More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...