Poster, Podium & Video Sessions
Presentation Authors: Masashi Honda*, Yusuke Kimura, Bunya Kawamoto, Panagiota Tsounapi, Katsuya Hikita, Yonago, Japan, Shogo Shimizu, Takahiro Shimizu, Motoaki Saito, Nankoku, Japan, Atsushi Takenaka, Yonago, Japan
Introduction: 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.
Source Of Funding: None
Department of Urology, Tottori University Faculty of Medicine
Masashi Honda, M.D., Ph.D.
Associate Professor in Div. of Urology, Dept. of Surgery, Tottori University Facluty of Medicine, Yonago, Japan
2017−present Associate Professor in Div. of Urology, Dept. of Surgery, Tottori University Faculty of Medicine.
2016−present Delegate of the Japanese Urological Association.
2016−present Delegate of the Japanese Society of Endourology.
2016−2017 Senior Assistant Professor in in Div. of Urology, Dept. of Surgery, Tottori University Faculty of Medicine.
2014−present Delegate of the Japanese Continence Society.
2011−2016 Senior Assistant Professor in Dept. of Urology, Tottori University Hospital.
2007−2011 Assistant Professor in Dept. of Urology, Tottori University Hospital.
2006−2007 Research Fellow in Dept. of Urology, University of Pittsburgh, Pittsburgh, USA.
2003−2006 Assistant Professor in Dept. of Urology, Tottori University Hospital.
1997−1998 Resident in Dept. of Urology, Tottori University Hospital.
Entered Tottori University Faculty of Medicine, April, 1991, and graduated March, 1997, with the degree of Bachelor of Medicine.
Obtained an M.D.. May, 1997.
Entered Dept. of Urology, Tottori University Graduate School of Medicine, April, 1998, and graduated March, 2002, with the degree of Ph.D.
2015 European Associaiton of Urology Annual Meeting 2015 Best of Posters
Tuesday, May 16
7:00 AM – 9:00 AM