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J Urol. 2013 Apr;189(4):1574-9. doi: 10.1016/j.juro.2012.09.095. Epub 2012 Sep 25.

Role of opioid and metabotropic glutamate 5 receptors in pudendal inhibition of bladder overactivity in cats.

Author information

1
Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Abstract

PURPOSE:

We determined the role of opioid and metabotropic glutamate 5 receptors in the pudendal inhibition of bladder overactivity.

MATERIALS AND METHODS:

Cystometrograms were performed in 11 cats under α-chloralose anesthesia by slowly infusing the bladder with saline or 0.25% acetic acid. Pudendal nerve stimulation at intensities of multiple times the threshold to induce observable anal twitching was applied during cystometrogram to inhibit the bladder overactivity induced by acetic acid irritation. Naloxone (0.1, 0.3 and 1 mg/kg intravenously) was administered to block opioid receptors, followed by MTEP (3 and 10 mg/kg intravenously) to block metabotropic glutamate 5 receptors. After each drug dose, pudendal inhibition of bladder overactivity was examined during cystometrogram.

RESULTS:

Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased mean ± SE bladder capacity to 23.6% ± 2.7% of saline control capacity. Pudendal nerve stimulation at 1 to 1.5 and 4 × threshold suppressed bladder overactivity and significantly increased mean capacity to 57.5% ± 8.1% (p = 0.0005) and 106% ± 15% (p = 0.0002), respectively, of saline control capacity. Naloxone had no effect on pudendal inhibition but MTEP eliminated the inhibition induced by low intensity stimulation and significantly decreased the inhibition induced by high intensity stimulation (p <0.05). Neither naloxone nor MTEP altered baseline bladder overactivity.

CONCLUSIONS:

Opioid receptors are not involved in pudendal inhibition of bladder overactivity but metabotropic glutamate 5 receptors are partially involved. Understanding neurotransmitter mechanisms could improve the efficacy of neuromodulation therapy for overactive bladder and identify molecular targets for developing new drugs for overactive bladder.

PMID:
23022006
PMCID:
PMC3690132
DOI:
10.1016/j.juro.2012.09.095
[Indexed for MEDLINE]
Free PMC Article

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