The Influence of an Adrenergic Antagonist Guanethidine (GUA) on the Distribution Pattern and Chemical Coding of Dorsal Root Ganglia (DRG) Neurons Supplying the Porcine Urinary Bladder

Int J Mol Sci. 2021 Dec 13;22(24):13399. doi: 10.3390/ijms222413399.

Abstract

Although guanethidine (GUA) was used in the past as a drug to suppress hyperactivity of the sympathetic nerve fibers, there are no available data concerning the possible action of this substance on the sensory component of the peripheral nervous system supplying the urinary bladder. Thus, the present study was aimed at disclosing the influence of intravesically instilled GUA on the distribution, relative frequency, and chemical coding of dorsal root ganglion neurons associated with the porcine urinary bladder. The investigated sensory neurons were visualized with a retrograde tracing method using Fast Blue (FB), while their chemical profile was disclosed with single-labeling immunohistochemistry using antibodies against substance P (SP), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP), galanin (GAL), neuronal nitric oxide synthase (nNOS), somatostatin (SOM), and calbindin (CB). After GUA treatment, a slight decrease in the number of FB+ neurons containing SP was observed when compared with untreated animals (34.6 ± 6.5% vs. 45.6 ± 1.3%), while the number of retrogradely traced cells immunolabeled for GAL, nNOS, and CB distinctly increased (12.3 ± 1.0% vs. 7.4 ± 0.6%, 11.9 ± 0.6% vs. 5.4 ± 0.5% and 8.6 ± 0.5% vs. 2.7 ± 0.4%, respectively). However, administration of GUA did not change the number of FB+ neurons containing CGRP, PACAP, or SOM. The present study provides evidence that GUA significantly modifies the sensory innervation of the porcine urinary bladder wall and thus may be considered a potential tool for studying the plasticity of this subdivision of the bladder innervation.

Keywords: dorsal root ganglia neurons; guanethidine; immunohistochemistry; neuropeptides; pig; sensory innervation; urinary bladder.

MeSH terms

  • Adrenergic Antagonists / pharmacology
  • Adrenergic Neurons / drug effects
  • Adrenergic Neurons / metabolism
  • Animals
  • Calbindins / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Female
  • Galanin / metabolism
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Guanethidine / metabolism
  • Guanethidine / pharmacology*
  • Neurotoxins / pharmacology
  • Nitric Oxide Synthase / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
  • Sensory Receptor Cells / metabolism
  • Somatostatin / metabolism
  • Substance P / metabolism
  • Swine
  • Urinary Bladder / drug effects
  • Urinary Bladder / innervation*

Substances

  • Adrenergic Antagonists
  • Calbindins
  • Neurotoxins
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Substance P
  • Somatostatin
  • Galanin
  • Nitric Oxide Synthase
  • Calcitonin Gene-Related Peptide
  • Guanethidine