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The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A(3) Receptor Agonist, in a Rat Model of Colitis

The pharmacological activation of A(3) receptors has shown potential usefulness in the management of bowel inflammation. However, the role of these receptors in the control of visceral hypersensitivity in the presence of intestinal inflammation has not been investigated. The effects of AR170, a pote...

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Autores principales: Antonioli, Luca, Lucarini, Elena, Lambertucci, Catia, Fornai, Matteo, Pellegrini, Carolina, Benvenuti, Laura, Di Cesare Mannelli, Lorenzo, Spinaci, Andrea, Marucci, Gabriella, Blandizzi, Corrado, Ghelardini, Carla, Volpini, Rosaria, Dal Ben, Diego
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348903/
https://www.ncbi.nlm.nih.gov/pubmed/32575844
http://dx.doi.org/10.3390/cells9061509
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author Antonioli, Luca
Lucarini, Elena
Lambertucci, Catia
Fornai, Matteo
Pellegrini, Carolina
Benvenuti, Laura
Di Cesare Mannelli, Lorenzo
Spinaci, Andrea
Marucci, Gabriella
Blandizzi, Corrado
Ghelardini, Carla
Volpini, Rosaria
Dal Ben, Diego
author_facet Antonioli, Luca
Lucarini, Elena
Lambertucci, Catia
Fornai, Matteo
Pellegrini, Carolina
Benvenuti, Laura
Di Cesare Mannelli, Lorenzo
Spinaci, Andrea
Marucci, Gabriella
Blandizzi, Corrado
Ghelardini, Carla
Volpini, Rosaria
Dal Ben, Diego
author_sort Antonioli, Luca
collection PubMed
description The pharmacological activation of A(3) receptors has shown potential usefulness in the management of bowel inflammation. However, the role of these receptors in the control of visceral hypersensitivity in the presence of intestinal inflammation has not been investigated. The effects of AR170, a potent and selective A(3) receptor agonist, and dexamethasone (DEX) were tested in rats with 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis to assess their tissue inflammatory parameters. The animals received AR170, DEX, or a vehicle intraperitoneally for 6 days, starting 1 day before the induction of colitis. Visceral pain was assessed by recording the abdominal responses to colorectal distension in animals with colitis. Colitis was associated with a decrease in body weight and an increase in spleen weight. The macroscopic damage score and tissue tumor necrosis factor (TNF), interleukin 1β (IL-1β), and myeloperoxidase (MPO) levels were also enhanced. AR170, but not DEX, improved body weight. Both drugs counteracted the increase in spleen weight, ameliorated macroscopic colonic damage, and decreased TNF, IL-1β, and MPO tissue levels. The enhanced visceromotor response (VMR) in rats with colitis was decreased via AR170 administration. In rats with colitis, AR170 counteracted colonic inflammatory cell infiltration and decreased pro-inflammatory cytokine levels, thereby relieving visceral hypersensitivity.
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spelling pubmed-73489032020-07-22 The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A(3) Receptor Agonist, in a Rat Model of Colitis Antonioli, Luca Lucarini, Elena Lambertucci, Catia Fornai, Matteo Pellegrini, Carolina Benvenuti, Laura Di Cesare Mannelli, Lorenzo Spinaci, Andrea Marucci, Gabriella Blandizzi, Corrado Ghelardini, Carla Volpini, Rosaria Dal Ben, Diego Cells Article The pharmacological activation of A(3) receptors has shown potential usefulness in the management of bowel inflammation. However, the role of these receptors in the control of visceral hypersensitivity in the presence of intestinal inflammation has not been investigated. The effects of AR170, a potent and selective A(3) receptor agonist, and dexamethasone (DEX) were tested in rats with 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis to assess their tissue inflammatory parameters. The animals received AR170, DEX, or a vehicle intraperitoneally for 6 days, starting 1 day before the induction of colitis. Visceral pain was assessed by recording the abdominal responses to colorectal distension in animals with colitis. Colitis was associated with a decrease in body weight and an increase in spleen weight. The macroscopic damage score and tissue tumor necrosis factor (TNF), interleukin 1β (IL-1β), and myeloperoxidase (MPO) levels were also enhanced. AR170, but not DEX, improved body weight. Both drugs counteracted the increase in spleen weight, ameliorated macroscopic colonic damage, and decreased TNF, IL-1β, and MPO tissue levels. The enhanced visceromotor response (VMR) in rats with colitis was decreased via AR170 administration. In rats with colitis, AR170 counteracted colonic inflammatory cell infiltration and decreased pro-inflammatory cytokine levels, thereby relieving visceral hypersensitivity. MDPI 2020-06-21 /pmc/articles/PMC7348903/ /pubmed/32575844 http://dx.doi.org/10.3390/cells9061509 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Antonioli, Luca
Lucarini, Elena
Lambertucci, Catia
Fornai, Matteo
Pellegrini, Carolina
Benvenuti, Laura
Di Cesare Mannelli, Lorenzo
Spinaci, Andrea
Marucci, Gabriella
Blandizzi, Corrado
Ghelardini, Carla
Volpini, Rosaria
Dal Ben, Diego
The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A(3) Receptor Agonist, in a Rat Model of Colitis
title The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A(3) Receptor Agonist, in a Rat Model of Colitis
title_full The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A(3) Receptor Agonist, in a Rat Model of Colitis
title_fullStr The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A(3) Receptor Agonist, in a Rat Model of Colitis
title_full_unstemmed The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A(3) Receptor Agonist, in a Rat Model of Colitis
title_short The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A(3) Receptor Agonist, in a Rat Model of Colitis
title_sort anti-inflammatory and pain-relieving effects of ar170, an adenosine a(3) receptor agonist, in a rat model of colitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348903/
https://www.ncbi.nlm.nih.gov/pubmed/32575844
http://dx.doi.org/10.3390/cells9061509
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