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Spinal glycine transporter-1 inhibition influences the micturition reflex in urethane-anesthetized rats

  • Urology - Original Paper
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Abstract

Purpose

Glycine is an inhibitory neurotransmitter in the central nervous system. So far, two types of glycine transporters (GlyTs), GlyT-1 and GlyT-2, have been cloned. The aim of this study is to investigate the effects of a selective GlyT-1 inhibitor that can increase endogenous glycine concentration on the micturition reflex in urethane-anesthetized rats.

Methods

Continuous cystometrograms (0.04 ml/min) were performed in female Sprague–Dawley rats (232–265 g) under urethane anesthesia. After stable micturition cycles were established, ALX5407, a selective GlyT-1 inhibitor, was administered intrathecally or intracerebroventricularly to evaluate changes in bladder activity. Cystometric parameters were recorded and compared before and after drug administration.

Results

Intrathecal administration of ALX5407 (1, 3, 10 and 30 μg) increased intercontraction intervals at doses of 3 μg or higher in a dose-dependent fashion. Intrathecal administration of ALX5407 (1, 3, 10 and 30 μg) also increased pressure threshold at doses of 3 μg or higher in a dose-dependent fashion. However, when ALX5407 (1, 3, 10 and 30 μg) was administered intracerebroventricularly, there were no significant changes in intercontraction intervals, pressure threshold, maximum voiding pressure or baseline pressure or post-void residual urine volume at any doses tested.

Conclusion

The results of our study indicate that GlyT-1 plays an important role in the modulation of micturition. Furthermore, these findings indicate that in urethane-anesthetized rats suppression of GlyT-1 can inhibit the micturition reflex at the spinal cord level. Thus, GlyT-1 could be a potential target for the treatment of bladder dysfunction such as overactive bladder.

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Acknowledgments

This study was funded by Grants from PVA 2793, DOD W81XWH-11-1-0763, and NIH DK088836.

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Authors and Affiliations

  1. Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan

    Masashi Honda, Katsuya Hikita, Bunya Kawamoto, Kuniyasu Muraoka, Takehiro Sejima & Atsushi Takenaka

  2. Department of Urology, University of Pittsburgh School of Medicine, Suite 700 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA

    Masashi Honda & Naoki Yoshimura

  3. Department of Pharmacology, Kochi University School of Medicine, Okocho Kohasu, Nankoku, 7838505, Japan

    Shogo Shimizu & Motoaki Saito

  4. Department of Urology, William Beaumont Hospital, 3535 W 13 Mile Rd #404, Royal Oak, MI, 48073, USA

    Michael B. Chancellor

Authors
  1. Masashi Honda
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  2. Katsuya Hikita
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  3. Bunya Kawamoto
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  4. Kuniyasu Muraoka
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  5. Shogo Shimizu
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  6. Motoaki Saito
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  7. Takehiro Sejima
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  8. Michael B. Chancellor
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  9. Naoki Yoshimura
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  10. Atsushi Takenaka
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Corresponding author

Correspondence to Naoki Yoshimura.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All experiments were conducted in accordance with NIH guidelines and approved by the University of Pittsburgh Institutional Animal Care and Use Committee.

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Honda, M., Hikita, K., Kawamoto, B. et al. Spinal glycine transporter-1 inhibition influences the micturition reflex in urethane-anesthetized rats. Int Urol Nephrol 48, 349–354 (2016). https://doi.org/10.1007/s11255-015-1148-0

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  • DOI: https://doi.org/10.1007/s11255-015-1148-0

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