ArticleThe American journal of pathology2013
Intestinal epithelial cell-derived μ-opioid signaling protects against ischemia reperfusion injury through PI3K signaling.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain - a randomised clinical study.Alimentary pharmacology & therapeutics · 2014Trial
- Shifted Balance Between Ventral Striatal Prodynorphin and Proenkephalin Biases Development of Cocaine Place Avoidance.Addiction biology · 2025Article
- Mu opioid receptors expressed in striatal D2 medium spiny neurons have divergent contributions to cocaine and morphine reward.Neuroscience · 2025Article
- Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.Clinical and translational medicine · 2025Review
- Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia-reperfusion injury.Liver research (Beijing, China) · 2024Article
- Corilagin alleviates intestinal ischemia/reperfusion injury by relieving oxidative stress and apoptosis via AMPK/Sirt1-autophagy pathway.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Opioid Use, Gut Dysbiosis, Inflammation, and the Nervous System.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Review
- Mu opioid receptors on vGluT2-expressing glutamatergic neurons modulate opioid reward.Addiction biology · 2021Article
- Current overview of opioids in progression of inflammatory bowel disease; pharmacological and clinical considerations.Molecular biology reports · 2021Review
- TNFAIP8 controls murine intestinal stem cell homeostasis and regeneration by regulating microbiome-induced Akt signaling.Nature communications · 2020Article
- Synapse-specific expression of mu opioid receptor long-term depression in the dorsomedial striatum.Scientific reports · 2020Article
- Exploring Morphine-Triggered PKC-Targets and Their Interaction with Signaling Pathways Leading to Pain via TrkA.Proteomes · 2018Review
- Alcohol exposure disrupts mu opioid receptor-mediated long-term depression at insular cortex inputs to dorsolateral striatum.Nature communications · 2018Article
- T-lymphocyte-derived enkephalins reduce TJournal of gastroenterology · 2018Article
- Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Murine Model of Intestinal Ischemia-reperfusion Injury.Journal of visualized experiments : JoVE · 2016Article
- The protective effect of hydromorphone to ischemia in rat glial cells.SpringerPlus · 2016Article
- Topical fentanyl stimulates healing of ischemic wounds in diabetic rats.Journal of diabetes · 2015Article
- Combined restitutive therapy for treatment of immunosuppressive refractory Crohn disease.Journal of pediatric gastroenterology and nutrition · 2015Article
- Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research.American journal of physiology. Gastrointestinal and liver physiology · 2015Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Intestinal ischemia has a wide variety of causes, including, but not limited to, atherosclerosis, thrombosis, hypotension, and chronic inflammation. In severe cases, ischemic injury can result in death. μ-Opioid receptor (MOR) signaling has previously been shown to protect against chemically induced colitis, but the cellular origin of this effect remains unknown. Herein, we evaluated the role of intestinal epithelial cell (IEC)-derived MOR signaling in host responses to ischemia/reperfusion-induced injury. Ileal ischemia was accomplished through obstruction of the distal branches of the superior mesenteric artery (60 minutes) and reperfusion for 90 minutes (ischemia-reperfusion). Floxed-MOR mice were crossed to Villin-cre transgenic mice to selectively delete the MOR gene in IECs (MOR(IEC-/-)). Radio-ligand binding assays demonstrated selective loss of MOR signaling in IECs of MOR(IEC-/-) mice. The s.c. administration of the MOR agonist, [D-Arg2, Lys4] dermorphin (1-4) amide (DALDA), 10 minutes before surgery protected against both ischemic and reperfusion phases of intestinal injury, an effect abolished in MOR(IEC-/-) mice. This cytoprotective effect was associated with enterocyte-mediated phosphoinositide 3-kinase (PI3K)/glycogen synthase kinase 3β signaling and decreased apoptosis, as determined by IHC and caspase-3 processing. PI3K blockade with Ly294002 resulted in loss of MOR-mediated cytoprotective function. Together, these data show that IEC-derived μ-opioid signaling uses the PI3K pathway to protect cells against the damaging effect of ischemia-reperfusion. Targeting MOR signaling may represent a novel mean to alleviate intestinal injury and promote the wound-healing response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.