ArticleInternational journal of molecular sciences2018
Selective Blockade of the Metabotropic Glutamate Receptor mGluR5 Protects Mouse Livers in In Vitro and Ex Vivo Models of Ischemia Reperfusion Injury.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Metabotropic Glutamate Receptor 3 Expression During Liver Disease Progression: Association with Inflammation and Cell Viability in Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- Complex I Modulator BI4500 Reduces MASH by Limiting Oxidative Stress and Reprogramming Lipid Metabolism via AMPK in MCD Rats.Antioxidants (Basel, Switzerland) · 2026Article
- MCD Diet Modulates HuR and Oxidative Stress-Related HuR Targets in Rats.International journal of molecular sciences · 2023Article
- MPEP Attenuates Intrahepatic Fat Accumulation in Obese Mice.International journal of molecular sciences · 2023Article
- NO-IL-6/10-IL-1β axis: a new pathway in steatotic and non-steatotic liver grafts from brain-dead donor rats.Frontiers in immunology · 2023Article
- Article
- Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death.International journal of molecular sciences · 2021Article
- Pathophysiologic Role of Neurotransmitters in Digestive Diseases.Frontiers in physiology · 2021Review
- The selective blockade of metabotropic glutamate receptor-5 attenuates fat accumulation in an <em>in vitro</em> model of benign steatosis.European journal of histochemistry : EJH · 2020Article
- Isolation of rat hepatocytes for pharmacological studies on metabotropic glutamate receptor (mGluR) subtype 5: a comparison between collagenase I versus collagenase IV.European journal of histochemistry : EJH · 2020Article
- Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis.Cell metabolism · 2019Article
- Molecular Mechanisms and Pathophysiology of Ischemia-Reperfusion Injury.International journal of molecular sciences · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
2-Methyl-6-(phenylethynyl)pyridine (MPEP), a negative allosteric modulator of the metabotropic glutamate receptor (mGluR) 5, protects hepatocytes from ischemic injury. In astrocytes and microglia, MPEP depletes ATP. These findings seem to be self-contradictory, since ATP depletion is a fundamental stressor in ischemia. This study attempted to reconstruct the mechanism of MPEP-mediated ATP depletion and the consequences of ATP depletion on protection against ischemic injury. We compared the effects of MPEP and other mGluR5 negative modulators on ATP concentration when measured in rat hepatocytes and acellular solutions. We also evaluated the effects of mGluR5 blockade on viability in rat hepatocytes exposed to hypoxia. Furthermore, we studied the effects of MPEP treatment on mouse livers subjected to cold ischemia and warm ischemia reperfusion. We found that MPEP and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) deplete ATP in hepatocytes and acellular solutions, unlike fenobam. This finding suggests that mGluR5s may not be involved, contrary to previous reports. MPEP, as well as MTEP and fenobam, improved hypoxic hepatocyte viability, suggesting that protection against ischemic injury is independent of ATP depletion. Significantly, MPEP protected mouse livers in two different ex vivo models of ischemia reperfusion injury, suggesting its possible protective deployment in the treatment of hepatic inflammatory conditions.
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