PMID- 22806643 OWN - NLM STAT- MEDLINE DCOM- 20130415 LR - 20211021 IS - 1097-4547 (Electronic) IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 90 IP - 11 DP - 2012 Nov TI - Protective role of mu opioid receptor activation in intestinal inflammation induced by mesenteric ischemia/reperfusion in mice. PG - 2146-53 LID - 10.1002/jnr.23108 [doi] AB - Intestinal ischemia is a clinical emergency with high morbidity and mortality. We investigated whether activation of mu opioid receptor (muOR) protects from the inflammation induced by intestinal ischemia and reperfusion (I/R) in mice. Ischemia was induced by occlusion of the superior mesenteric artery (45 min), followed by reperfusion (5 hr). Sham-operated (SO) and normal (N) mice served as controls. Each group received subcutaneously 1) saline solution, 2) the muOR selective agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO; 0.01 mg kg(-1) ), 3) DAMGO and the selective muOR antagonist [H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2] (CTAP; 0.1 mg kg(-1) ), or 4) CTAP alone. I/R induced intestinal inflammation as indicated by histological damage and the significant increase in myeloperoxidase (MPO) activity, an index of tissue neutrophil accumulation. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) mRNA levels were also increased in I/R mice compared with SO. DAMGO significantly reduced tissue damage, MPO activity, and TNF-alpha mRNA levels in I/R, and these effects were reversed by CTAP. By contrast, DAMGO did not modify IL-10 mRNA levels or gastrointestinal transit. DAMGO's effects are receptor mediated and likely are due to activation of peripheral muORs, because it does not readily cross the blood-brain barrier. These findings suggest that activation of peripheral muOR protects from the inflammatory response induced by I/R through a pathway involving the proinflammatory cytokine TNF-alpha. Reduction of acute inflammation might prevent I/R complications, including motility impairment, which develop at a later stage of reperfusion and likely are due to inflammatory cell infiltrates. CI - Copyright (c) 2012 Wiley Periodicals, Inc. FAU - Saccani, Francesca AU - Saccani F AD - Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA. FAU - Anselmi, Laura AU - Anselmi L FAU - Jaramillo, Ingrid AU - Jaramillo I FAU - Bertoni, Simona AU - Bertoni S FAU - Barocelli, Elisabetta AU - Barocelli E FAU - Sternini, Catia AU - Sternini C LA - eng GR - DK41301/DK/NIDDK NIH HHS/United States GR - R56 DK054155/DK/NIDDK NIH HHS/United States GR - P30 DK041301/DK/NIDDK NIH HHS/United States GR - DK54155/DK/NIDDK NIH HHS/United States GR - R01 DK054155/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120717 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Cytokines) RN - 0 (Receptors, Opioid, mu) SB - IM MH - Animals MH - Cytokines/biosynthesis MH - Female MH - Inflammation/etiology/*metabolism/pathology MH - Intestinal Mucosa/*metabolism MH - Intestines/blood supply/pathology MH - Mesentery/blood supply MH - Mice MH - Mice, Inbred C57BL MH - Real-Time Polymerase Chain Reaction MH - Receptors, Opioid, mu/*metabolism MH - Reperfusion Injury/complications/*metabolism/pathology MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC3439549 MID - NIHMS384620 EDAT- 2012/07/19 06:00 MHDA- 2013/04/16 06:00 PMCR- 2013/11/01 CRDT- 2012/07/19 06:00 PHST- 2011/09/20 00:00 [received] PHST- 2012/05/27 00:00 [revised] PHST- 2012/05/31 00:00 [accepted] PHST- 2012/07/19 06:00 [entrez] PHST- 2012/07/19 06:00 [pubmed] PHST- 2013/04/16 06:00 [medline] PHST- 2013/11/01 00:00 [pmc-release] AID - 10.1002/jnr.23108 [doi] PST - ppublish SO - J Neurosci Res. 2012 Nov;90(11):2146-53. doi: 10.1002/jnr.23108. Epub 2012 Jul 17.