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Roles of the spinal glutamatergic pathway activated through α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and its interactions with spinal noradrenergic and serotonergic pathways in the rat urethral continence mechanisms

Authors

  • Naoki Kawamorita,

    1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    2. Department of Urology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan
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  • Yasuhiro Kaiho,

    1. Department of Urology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan
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  • Minoru Miyazato,

    1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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  • Yoichi Arai,

    1. Department of Urology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan
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  • Naoki Yoshimura

    Corresponding author
    1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • Correspondence to: Naoki Yoshimura, Department of Urology, University of Pittsburgh School of Medicine, Suite 700, Kaufmann Medical Building, 3471 Fifth Ave., Pittsburgh, PA 15213. E-mail: nyos@pitt.edu

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  • Lori Birder led the peer-review process as the Associate Editor responsible for the paper.
  • Conflict of interest: none.

Abstract

Aims

To investigate the role of the glutamatergic pathway and its relationship to noradrenergic and serotonergic pathways in modulation of the urethral continence reflex during sneezing in rats.

Methods

In female Sprague-Dawley rats under urethane anesthesia, the effects of an α-amino-3-hydroxy-5-meth-ylisoxazole-4-propionic acid (AMPA) glutamate receptor antagonist, a norepinephrine reuptake inhibitor and a serotonin [5-hydeoxytripitamine (5-HT)]2B/2C agonist on the amplitude of urethral responses during sneezing (AURS), urethral baseline pressure (UBP), and sneeze-induced leak point pressure (S-LPP) were investigated.

Results

Intrathecal application (i.t.) of NBQX disodium salt (an AMPA receptor antagonist) decreased AURS dose-dependently by approximately 60% without affecting UBP and caused stress urinary incontinence (SUI) during sneezing in 60% of normal rats. Nisoxetine (i.t.), a norepinephrine reuptake inhibitor, and mCPP (i.t.), a 5-HT2B/2C, agonist increased AURS, and NBQX (i.t.) abolished these excitatory effects of nisoxetine (i.t.) and mCPP (i.t.), whereas nisoxetine (i.t.) and mCPP (i.t.) did not enhance AURS in the presence of NBQX (i.t.).

Conclusion

These results indicate that the glutamatergic pathway acting through AMPA receptors plays a crucial role on the active urethral closure reflex during sneezing at the spinal level, and noradrenergic and serotonergic pathways modulate the reflex via the spinal glutamatergic system in rats. Neurourol. Urodynam. 34:475–481, 2015. © 2014 Wiley Periodicals, Inc.

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