Changes in nitrergic and tachykininergic pathways in rat proximal colon in response to chronic treatment with otilonium bromide

G. Cipriani, S. J. Gibbons, S. A. Saravanaperumal, J. Malysz, L. Sha, J. H. Szurszewski, David R Linden, S. Evangelista, M. S. Faussone-Pellegrini, M. G. Vannucchi, Gianrico Farrugia

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Otilonium bromide (OB) is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well-characterized, little is known about the effects of chronic administration of OB on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (ICC), key regulators of the gut function. Methods: Adult Sprague-Dawley rats were treated with OB in drinking water at a dose of 2 mg/kg for 30 days. The colons of OB-treated and age-matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (IR) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology. Key Results: Using immunohistochemistry, chronic OB administration did not change total neuron number, assessed by anti-Hu IR, but resulted in a significant increase in NK1 receptor positive neurons, a decrease in neuronal nitric oxide synthase expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. Chronic OB administration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonic ICC, detected by Kit IR, were not altered nor were slow waves or smooth muscle membrane potential. Conclusions & Inferences: Chronic treatment with OB caused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon.

Original languageEnglish (US)
Pages (from-to)997-1009
Number of pages13
JournalNeurogastroenterology and Motility
Volume27
Issue number7
DOIs
StatePublished - Jul 1 2015

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Colon
Myenteric Plexus
Interstitial Cells of Cajal
Neurons
Therapeutics
Nitrergic Neurons
Immunohistochemistry
Parasympatholytics
Nitric Oxide Synthase Type I
Irritable Bowel Syndrome
Electrophysiology
Microelectrodes
Substance P
octylonium
Nerve Fibers
Evoked Potentials
Synaptic Transmission
Drinking Water
Membrane Potentials
Electric Stimulation

Keywords

  • Antispasmodic
  • Confocal microscopy
  • Enteric nervous system
  • Excitability
  • Interstitial cells of Cajal
  • Junction potential
  • Myenteric plexus
  • Nerve-evoked activity
  • Slow wave

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

Changes in nitrergic and tachykininergic pathways in rat proximal colon in response to chronic treatment with otilonium bromide. / Cipriani, G.; Gibbons, S. J.; Saravanaperumal, S. A.; Malysz, J.; Sha, L.; Szurszewski, J. H.; Linden, David R; Evangelista, S.; Faussone-Pellegrini, M. S.; Vannucchi, M. G.; Farrugia, Gianrico.

In: Neurogastroenterology and Motility, Vol. 27, No. 7, 01.07.2015, p. 997-1009.

Research output: Contribution to journalArticle

Cipriani, G, Gibbons, SJ, Saravanaperumal, SA, Malysz, J, Sha, L, Szurszewski, JH, Linden, DR, Evangelista, S, Faussone-Pellegrini, MS, Vannucchi, MG & Farrugia, G 2015, 'Changes in nitrergic and tachykininergic pathways in rat proximal colon in response to chronic treatment with otilonium bromide', Neurogastroenterology and Motility, vol. 27, no. 7, pp. 997-1009. https://doi.org/10.1111/nmo.12576
Cipriani, G. ; Gibbons, S. J. ; Saravanaperumal, S. A. ; Malysz, J. ; Sha, L. ; Szurszewski, J. H. ; Linden, David R ; Evangelista, S. ; Faussone-Pellegrini, M. S. ; Vannucchi, M. G. ; Farrugia, Gianrico. / Changes in nitrergic and tachykininergic pathways in rat proximal colon in response to chronic treatment with otilonium bromide. In: Neurogastroenterology and Motility. 2015 ; Vol. 27, No. 7. pp. 997-1009.
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abstract = "Background: Otilonium bromide (OB) is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well-characterized, little is known about the effects of chronic administration of OB on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (ICC), key regulators of the gut function. Methods: Adult Sprague-Dawley rats were treated with OB in drinking water at a dose of 2 mg/kg for 30 days. The colons of OB-treated and age-matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (IR) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology. Key Results: Using immunohistochemistry, chronic OB administration did not change total neuron number, assessed by anti-Hu IR, but resulted in a significant increase in NK1 receptor positive neurons, a decrease in neuronal nitric oxide synthase expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. Chronic OB administration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonic ICC, detected by Kit IR, were not altered nor were slow waves or smooth muscle membrane potential. Conclusions & Inferences: Chronic treatment with OB caused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon.",
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T1 - Changes in nitrergic and tachykininergic pathways in rat proximal colon in response to chronic treatment with otilonium bromide

AU - Cipriani, G.

AU - Gibbons, S. J.

AU - Saravanaperumal, S. A.

AU - Malysz, J.

AU - Sha, L.

AU - Szurszewski, J. H.

AU - Linden, David R

AU - Evangelista, S.

AU - Faussone-Pellegrini, M. S.

AU - Vannucchi, M. G.

AU - Farrugia, Gianrico

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Background: Otilonium bromide (OB) is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well-characterized, little is known about the effects of chronic administration of OB on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (ICC), key regulators of the gut function. Methods: Adult Sprague-Dawley rats were treated with OB in drinking water at a dose of 2 mg/kg for 30 days. The colons of OB-treated and age-matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (IR) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology. Key Results: Using immunohistochemistry, chronic OB administration did not change total neuron number, assessed by anti-Hu IR, but resulted in a significant increase in NK1 receptor positive neurons, a decrease in neuronal nitric oxide synthase expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. Chronic OB administration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonic ICC, detected by Kit IR, were not altered nor were slow waves or smooth muscle membrane potential. Conclusions & Inferences: Chronic treatment with OB caused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon.

AB - Background: Otilonium bromide (OB) is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well-characterized, little is known about the effects of chronic administration of OB on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (ICC), key regulators of the gut function. Methods: Adult Sprague-Dawley rats were treated with OB in drinking water at a dose of 2 mg/kg for 30 days. The colons of OB-treated and age-matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (IR) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology. Key Results: Using immunohistochemistry, chronic OB administration did not change total neuron number, assessed by anti-Hu IR, but resulted in a significant increase in NK1 receptor positive neurons, a decrease in neuronal nitric oxide synthase expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. Chronic OB administration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonic ICC, detected by Kit IR, were not altered nor were slow waves or smooth muscle membrane potential. Conclusions & Inferences: Chronic treatment with OB caused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon.

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KW - Confocal microscopy

KW - Enteric nervous system

KW - Excitability

KW - Interstitial cells of Cajal

KW - Junction potential

KW - Myenteric plexus

KW - Nerve-evoked activity

KW - Slow wave

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JO - Neurogastroenterology and Motility

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