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Effects of sensory neuron-specific receptor agonist on bladder function in a rat model of cystitis induced by cyclophosphamide
Authors:Masashi Honda  Naoki Yoshimura  Bunya Kawamoto  Naoto Kobayashi  Katsuya Hikita  Kuniyasu Muraoka  Motoaki Saito  Takehiro Sejima  Michael B. Chancellor  Atsushi Takenaka
Affiliation:1. Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan
2. Department of Urology, University of Pittsburgh School of Medicine, Suite 700 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA
3. Department of Pharmacology, Kochi University School of Medicine, Okocho Kohasu, Nankoku, 7838505, Japan
4. Department of Urology, William Beaumont Hospital, 3535?W 13 Mile Rd #404, Royal Oak, MI, 48073, USA
Abstract:

Purpose

To investigate the effects of activation of sensory neuron-specific receptors (SNSRs) on cyclophosphamide (CYP) bladder overactivity in rats.

Methods

Female Sprague–Dawley rats (235–258 g) were used. Rats were injected with either CYP (200 mg/kg, intraperitoneally) or saline (control). Continuous cystometrograms (0.04 ml/min) were recorded 48 h after CYP or saline injection under urethane anesthesia. After stable micturition cycles were established, a selective rat SNSR1 agonist, bovine adrenal medulla 8-22 (BAM8-22), was administered intravenously or intrathecally.

Results

Cyclophosphamide treatment-induced higher baseline pressure and shorter intercontraction intervals compared with the control group. Intravenous administration of BAM8-22 at 10, 30 and 100 μg/kg significantly increased intercontraction intervals in the CYP-treated group. Intrathecal administration of BAM8-22 at 0.03, 0.1 and 0.3 μg also significantly increased intercontraction intervals in the CYP-treated group. Intravenous or intrathecal administration of BAM8-22 did not change baseline pressure or maximum voiding pressure in the CYP-treated group.

Conclusions

These findings indicate that activation of SNSRs can suppress CYP-induced bladder overactivity, probably due to suppression of bladder afferent activity.
Keywords:
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