The Influence of Resiniferatoxin (RTX) and Tetrodotoxin (TTX) on the Distribution, Relative Frequency, and Chemical Coding of Noradrenergic and Cholinergic Nerve Fibers Supplying the Porcine Urinary Bladder Wall

Ewa Lepiarczyk,Agnieszka Bossowska,Marta Majewska,Agnieszka Skowrońska,Mariusz Majewski,Jerzy Kaleczyc,Michal Majewski

doi:10.3390/toxins9100310

Ewa Lepiarczyk, Agnieszka Bossowska + Show 5 more

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https://doi.org/10.3390/toxins9100310

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Journal: Toxins	Publication Date: Oct 3, 2017
Citations: 10	License type: CC BY 4.0

Affiliation: University of Warmia and Mazury in Olsztyn

Abstract

The present study investigated the influence of intravesically instilled resiniferatoxin (RTX) or tetrodotoxin (TTX) on the distribution, number, and chemical coding of noradrenergic and cholinergic nerve fibers (NF) supplying the urinary bladder in female pigs. Samples from the bladder wall were processed for double-labelling immunofluorescence with antibodies against cholinergic and noradrenergic markers and some other neurotransmitter substances. Both RTX and TTX caused a significant decrease in the number of cholinergic NF in the urinary bladder wall (in the muscle coat, submucosa, and beneath the urothelium). RTX instillation resulted in a decrease in the number of noradrenergic NF in the submucosa and urothelium, while TTX treatment caused a significant increase in the number of these axons in all the layers. The most remarkable changes in the chemical coding of the NF comprised a distinct decrease in the number of the cholinergic NF immunoreactive to CGRP (calcitonin gene-related peptide), nNOS (neuronal nitric oxide synthase), SOM (somatostatin) or VIP (vasoactive intestinal polypeptide), and an increase in the number of noradrenergic NF immunopositive to GAL (galanin) or nNOS, both after RTX or TTX instillation. The present study is the first to suggest that both RTX and TTX can modify the number of noradrenergic and cholinergic NF supplying the porcine urinary bladder.

Highlights

Overactive bladder (OAB) is a condition characterized by the presence of urinary urgency, typically accompanied by nocturia and frequency, in the absence of urinary tract infection or another evident pathology
In our previous study [5], we found that botulinum toxin (BTX) strongly influences immunohistochemical characteristics of noradrenergic and cholinergic axons distributed in the porcine urinary bladder wall
The results of the present study clearly indicate, that application of either TTX or RTX is followed by meaningful changes in the distribution, relative frequency, and chemical coding of noradrenergic and cholinergic nerve fibers (NF) supplying the wall of the porcine urinary bladder

Summary

Introduction

Overactive bladder (OAB) is a condition characterized by the presence of urinary urgency, typically accompanied by nocturia and frequency, in the absence of urinary tract infection or another evident pathology. Toxins 2017, 9, 310 receptors by acetylcholine (ACh) released from parasympathetic/cholinergic neurons supplying the organ (for review see: [2]), antimuscarinic drugs are the treatment of choice in OAB. Their use is often unsatisfactory because of many associating side effects, such as dry mouth, cognitive changes, constipation, urinary retention, or blurred vision, resulting from the widespread blockade of cholinergic activity [3]. The most well-known neurotoxins, which have been successfully applied in urology, are botulinum toxin (BTX) and resiniferatoxin (RTX) (for review see: [4])

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