Involvement of 5-HT1B/1D receptors in the inflammatory response and oxidative stress in intestinal ischemia/reperfusion in rats.
Animals
Calcitonin Gene-Related Peptide
/ metabolism
Ileum
/ drug effects
Inflammation
/ metabolism
Intestinal Mucosa
/ drug effects
Male
Mesenteric Ischemia
/ metabolism
Oxadiazoles
/ pharmacology
Oxidative Stress
/ drug effects
Piperazines
/ pharmacology
Rats, Wistar
Receptor, Serotonin, 5-HT1B
/ metabolism
Receptor, Serotonin, 5-HT1D
/ metabolism
Reperfusion Injury
/ metabolism
Serotonin
/ metabolism
Serotonin 5-HT1 Receptor Agonists
/ pharmacology
Serotonin Antagonists
/ pharmacology
Sumatriptan
/ pharmacology
5-HT1B/1D receptor
Inflammation
Intestinal ischemia/reperfusion
Oxidative stress
Rat
Sumatriptan
Journal
European journal of pharmacology
ISSN: 1879-0712
Titre abrégé: Eur J Pharmacol
Pays: Netherlands
ID NLM: 1254354
Informations de publication
Date de publication:
05 Sep 2020
05 Sep 2020
Historique:
received:
26
02
2020
revised:
04
06
2020
accepted:
08
06
2020
pubmed:
24
6
2020
medline:
14
5
2021
entrez:
24
6
2020
Statut:
ppublish
Résumé
Acute mesenteric ischemia (AMI) is caused by an abrupt cessation of blood flow to the small intestine. Reperfusion is the return of blood flow to the ischemic bowel. Intestinal ischemia/reperfusion (I/R) leads to the formation of reactive oxygen species, local inflammatory response, and may lead to the patient's death. Pre-treatment of the intestinal may reduce the high mortality associated with AMI. 5-Hydroxytryptamine 1B (5-HT1B) and 5-HT1D receptors have anti-inflammatory and neuroprotective effects in different experimental studies. We aimed to investigate the potential involvement of these receptors in intestinal I/R injury. Firstly, we assessed the expression and localization of 5-HT1B and 5-HT1D receptors in the enteric nervous system using an immunofluorescence-based method. Intestinal I/R in rats was induced by 30 min occlusion of superior mesenteric artery and reperfusion for 2 h. Rats were randomly divided in different control and I/R groups (n = 6) receiving either vehicle, sumatriptan (5-HT1B/1D receptors agonist; 0.1 mg/kg), GR127,935 (5-HT1B/1D receptors antagonist; 0.1 mg/kg) and combination of sumatriptan (0.1 mg/kg) + GR127,935 (0.1 mg/kg) before determination of biochemical and histological parameters. In the enteric nervous system, 5-HT1B and 5-HT1D receptors were expressed 17% and 11.5%, respectively. Pre-treatment with sumatriptan decreased 5-hydroxytryptamine (5HT) level by 53%, and significantly decreased calcitonin gene-related peptide (CGRP) levels, lipid pereoxidation, neutrophil infiltration, and level of pro-inflammatory markers in the serum. Histopathologic studies also showed a remarkable decrease in intestinal tissue injury. These findings suggest that sumatriptan may inhibit intestinal injury induced by I/R through modulating the inflammatory response by activation of 5-HT1B/1D receptors.
Identifiants
pubmed: 32574671
pii: S0014-2999(20)30357-5
doi: 10.1016/j.ejphar.2020.173265
pii:
doi:
Substances chimiques
Oxadiazoles
0
Piperazines
0
Receptor, Serotonin, 5-HT1B
0
Receptor, Serotonin, 5-HT1D
0
Serotonin 5-HT1 Receptor Agonists
0
Serotonin Antagonists
0
GR 127935
2LLH6CEB40
Serotonin
333DO1RDJY
Sumatriptan
8R78F6L9VO
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
173265Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.