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

Toxins (Basel). 2017 Oct 3;9(10):310. doi: 10.3390/toxins9100310.

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.

Keywords: immunohistochemistry; nerve fibers; pig; resiniferatoxin; tetrodotoxin; urinary bladder.

MeSH terms

  • Adrenergic Fibers / drug effects*
  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Cholinergic Fibers / drug effects*
  • Diterpenes / pharmacology*
  • Female
  • Galanin / metabolism
  • Neuropeptide Y / metabolism
  • Nitric Oxide Synthase Type I / metabolism
  • Somatostatin / metabolism
  • Swine
  • Tetrodotoxin / pharmacology*
  • Urinary Bladder / drug effects*
  • Urinary Bladder / innervation
  • Urinary Bladder / metabolism
  • Vasoactive Intestinal Peptide / metabolism
  • Vesicular Acetylcholine Transport Proteins / metabolism

Substances

  • Diterpenes
  • Neuropeptide Y
  • Vesicular Acetylcholine Transport Proteins
  • Vasoactive Intestinal Peptide
  • Tetrodotoxin
  • Somatostatin
  • Galanin
  • resiniferatoxin
  • Nitric Oxide Synthase Type I
  • Calcitonin Gene-Related Peptide