ArticleThe Journal of pharmacology and experimental therapeutics2012
The role of β-arrestin2 in the mechanism of morphine tolerance in the mouse and guinea pig gastrointestinal tract.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Opioid-Induced Constipation: Mechanistic Insights, Experimental Models, and Future Perspectives.Biomedicines · 2026Review
- BR-bombesin: a novel bombesin-related peptide from the skin secretion of the Chaco tree frog (Boana raniceps) with physiological gastric effects.Amino acids · 2022Article
- Spoken and Unspoken Matters Regarding the Use of Opioids in Cancer.Journal of pain research · 2022Review
- The Guts of the Opioid Crisis.Physiology (Bethesda, Md.) · 2021Article
- Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel.Advances in therapy · 2021Review
- μ-Opioid Receptor-Mediated Enteric Glial Activation Is Involved in Morphine-Induced Constipation.Molecular neurobiology · 2021Article
- Mu and Delta Opioid Receptors Are Coexpressed and Functionally Interact in the Enteric Nervous System of the Mouse Colon.Cellular and molecular gastroenterology and hepatology · 2020Article
- Agonist-dependent development of delta opioid receptor tolerance in the colon.Cellular and molecular life sciences : CMLS · 2019Article
- G-Protein-Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases.Gastroenterology · 2019Review
- The Utilization of Mu-Opioid Receptor Biased Agonists: Oliceridine, an Opioid Analgesic with Reduced Adverse Effects.Current pain and headache reports · 2019Review
- Methylation Products of 6β- N-Heterocyclic Substituted Naltrexamine Derivatives as Potential Peripheral Opioid Receptor Modulators.ACS chemical neuroscience · 2018Article
- Inflammation-associated changes in DOR expression and function in the mouse colon.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- The gut-brain interaction in opioid tolerance.Current opinion in pharmacology · 2017Review
- Effects of acute and repeated treatment with the biased mu opioid receptor agonist TRV130 (oliceridine) on measures of antinociception, gastrointestinal function, and abuse liability in rodents.Journal of psychopharmacology (Oxford, England) · 2017Article
- Insights into the Role of Opioid Receptors in the GI Tract: Experimental Evidence and Therapeutic Relevance.Handbook of experimental pharmacology · 2017Review
- cPKCγ membrane translocation is involved in herkinorin‑induced neuroprotection against cerebral ischemia/reperfusion injury in mice.Molecular medicine reports · 2017Article
- 6β-N-Heterocyclic Substituted Naltrexamine Derivative BNAP: A Peripherally Selective Mixed MOR/KOR Ligand.ACS chemical neuroscience · 2016Article
- Human native kappa opioid receptor functions not predicted by recombinant receptors: Implications for drug design.Scientific reports · 2016Article
- Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- The Impact of Opioid Treatment on Regional Gastrointestinal Transit.Journal of neurogastroenterology and motility · 2016Article
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Authors and funding
6 authors.
Funding
Abstract
β-Arrestin2 has been reported to play an essential role in analgesic tolerance. Analgesic tolerance without concomitant tolerance to constipation is a limiting side effect of chronic morphine treatment. Because tolerance to morphine develops in the mouse ileum but not the colon, we therefore examined whether the role of β-arrestin2 in the mechanism of morphine tolerance differs in the ileum and colon. In both guinea pig and mouse, chronic in vitro exposure (2 h, 10 μM) to morphine resulted in tolerance development in the isolated ileum but not the colon. The IC(50) values for morphine-induced inhibition of electrical field stimulation contraction of guinea pig longitudinal muscle myenteric plexus shifted rightward in the ileum from 5.7 ± 0.08 (n = 9) to 5.45 ± 0.09 (n = 6) (p < 0.001) after morphine exposure. A significant shift was not observed in the colon. Similar differential tolerance was seen between the mouse ileum and the colon. However, tolerance developed in the colon from β-arrestin2 knockout mice. β-Arrestin2 and extracellular signal-regulated kinase 1/2 expression levels were determined further by Western blot analyses in guinea pig longitudinal muscle myenteric plexus. A time-dependent decrease in the expression of β-arrestin2 and extracellular signal-regulated kinase 1/2 occurred in the ileum but not the colon after 2 h of morphine (10 μM) exposure. Naloxone prevented the decrease in β-arrestin2. In the isolated ileum from guinea pigs chronically treated in vivo with morphine for 7 days, neither additional tolerance to in vitro exposure of morphine nor a decrease in β-arrestin2 occurred. We conclude that a decrease in β-arrestin2 is associated with tolerance development to morphine in the gastrointestinal tract.
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