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Anandamide transporter-mediated regulation of the micturition reflex in urethane-anesthetized rats

  • Urology - Original Paper
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Abstract

Purpose

The aim of this study was to investigate the effects of an anandamide transporter inhibitor that can increase endogenous anandamide concentration on the micturition reflex in urethane-anesthetized rats.

Methods

Continuous cystometrograms were performed in female Sprague–Dawley rats under urethane anesthesia. After stable micturition cycles were established, VDM11 (1, 3 and 10 mg/kg), an anandamide membrane transporter inhibitor, was administered intravenously to evaluate changes in bladder activity. In experiments examining the effects of cannabinoid (CB) receptor antagonists, VDM11 (10 mg/kg) was injected intravenously when the first bladder contraction was observed after intravenous administration of AM251, a CB1 receptor antagonist (3 mg/kg), or AM630, a CB2 receptor antagonist (3 mg/kg).

Results

Intravenous administration of VDM11 increased intercontraction intervals and threshold pressure at doses of 3 mg/kg or higher in dose-dependent fashion. 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 observed, as they were after VDM11 alone.

Conclusion

These results suggest that anandamide, an endogenous CB ligand, can modulate the micturition reflex and that anandamide transporters play an important role in this modulation. In urethane-anesthetized rats, inhibition of the uptake of anandamide can inhibit the micturition reflex and these inhibitory effects of VDM11 are at least in part mediated by the CB1 receptor.

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Acknowledgments

This study was funded by Grants from PVA 2793 and NIH DK088836.

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Authors and Affiliations

  1. Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 6838504, Japan

    Masashi Honda, Bunya Kawamoto, Katsuya Hikita, Kuniyasu Muraoka & 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 Medical School, 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

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  1. Masashi Honda
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  2. Naoki Yoshimura
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  3. Bunya Kawamoto
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  4. Katsuya Hikita
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  6. Shogo Shimizu
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  7. Motoaki Saito
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  8. Michael B. Chancellor
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  9. 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., Yoshimura, N., Kawamoto, B. et al. Anandamide transporter-mediated regulation of the micturition reflex in urethane-anesthetized rats. Int Urol Nephrol 48, 1407–1412 (2016). https://doi.org/10.1007/s11255-016-1329-5

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  • DOI: https://doi.org/10.1007/s11255-016-1329-5

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