We hypothesized that proteinase-activated receptor-2 (PAR2) modulates intestinal injuries induced by ischemia/reperfusion. Ischemia (1 hour) plus reperfusion (6 hours) significantly delayed gastrointestinal transit (GIT) compared with sham operation. Intraduodenal injection of PAR2- activating peptide SLIGRL-NH2 significantly accelerated transit in ischemia/reperfusion but not in sham-operated rats. GIT was significantly delayed in ischemia/reperfusion and sham-operated PAR2 -/- mice compared with PAR2 -/-. SLIGRL-NH2 significantly accelerated transit in ischemia/reperfusion in PAR2 -/- but not in PAR2 -/- mice. Prevention of mast cell degranulation with cromolyn, ablation of visceral afferente with capsaicin, and antagonism of calcitonin generelated peptide (CGRP) and neurokinin-1 receptors with CGRP8–37 and RP67580, respectively, abolished the SLIGRL-NH2-induced stimulatory effect on transit in ischemia/reperfusion. Tissue damage was significantly reduced by SLIGRL-NH2; this effect was not observed in cromolyn-, capsaicin-, or RP67580-treated rats but was detected following CGRP8– 37. Intestinal PAR2 mRNA levels were not affected by SLIGRL-NH2 in ischemia/reperfusion. We propose that PAR2 modulates GIT and tissue damage in intestinal ischemia/reperfusion by a mechanism dependent on mast cells and visceral afferents. PAR2 effect on transit might be mediated by CGRP and substance P, whereas the effect on tissue damage appears to involve substance P but not CGRP. PAR2 might be a signaling system in the neuroimmune communication in intestinal ischemia/reperfusion. Am J Pathol 2006, 169:177–188

Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents / Cattaruzza, Fiore; Cenac, N; Barocelli, Elisabetta; Impicciatore, Mariannina; Hyun, E; Vergnolle, N; Sternini, C.. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 169:(2006), pp. 177-188. [10.2353/ajpath.2006.051098]

Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents

CATTARUZZA, Fiore;BAROCELLI, Elisabetta;IMPICCIATORE, Mariannina;
2006-01-01

Abstract

We hypothesized that proteinase-activated receptor-2 (PAR2) modulates intestinal injuries induced by ischemia/reperfusion. Ischemia (1 hour) plus reperfusion (6 hours) significantly delayed gastrointestinal transit (GIT) compared with sham operation. Intraduodenal injection of PAR2- activating peptide SLIGRL-NH2 significantly accelerated transit in ischemia/reperfusion but not in sham-operated rats. GIT was significantly delayed in ischemia/reperfusion and sham-operated PAR2 -/- mice compared with PAR2 -/-. SLIGRL-NH2 significantly accelerated transit in ischemia/reperfusion in PAR2 -/- but not in PAR2 -/- mice. Prevention of mast cell degranulation with cromolyn, ablation of visceral afferente with capsaicin, and antagonism of calcitonin generelated peptide (CGRP) and neurokinin-1 receptors with CGRP8–37 and RP67580, respectively, abolished the SLIGRL-NH2-induced stimulatory effect on transit in ischemia/reperfusion. Tissue damage was significantly reduced by SLIGRL-NH2; this effect was not observed in cromolyn-, capsaicin-, or RP67580-treated rats but was detected following CGRP8– 37. Intestinal PAR2 mRNA levels were not affected by SLIGRL-NH2 in ischemia/reperfusion. We propose that PAR2 modulates GIT and tissue damage in intestinal ischemia/reperfusion by a mechanism dependent on mast cells and visceral afferents. PAR2 effect on transit might be mediated by CGRP and substance P, whereas the effect on tissue damage appears to involve substance P but not CGRP. PAR2 might be a signaling system in the neuroimmune communication in intestinal ischemia/reperfusion. Am J Pathol 2006, 169:177–188
2006
Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents / Cattaruzza, Fiore; Cenac, N; Barocelli, Elisabetta; Impicciatore, Mariannina; Hyun, E; Vergnolle, N; Sternini, C.. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 169:(2006), pp. 177-188. [10.2353/ajpath.2006.051098]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1507365
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