Principal Investigator: Andrea Ferrigno

The metabotropic glutamate (mGlu) receptor-type 5, a G protein-coupled receptor, is one of the more researched proteins because of its role in many conditions of the central nervous system, such as pain, depression, addiction and fragile X syndrome.
In previous researches, we found that hepatocytes express the mGlu5 receptor. Furthermore, we discovered that this receptor has a permissive role in the modulation of ischemic and free radical liver injury: mGlu5 receptor allosteric negative modulators improve hepatocytes viability in warm ischemia and reduce free radical formation in hepatocytes treated with tert-butyl hydroperoxide. Currently, we are trying to elucidate the molecular mechanisms involved in these processes, by investigating the state of different pathways involved in inflammation, apoptosis and necrosis, after the activation/blocking of mGlu5 receptor. To accomplish this goal, we use in vitro and ex vivo models of hepatic injury, such as: rodent primary hepatocytes exposed to hypoxic conditions at 37°C or rodent models of cold preservation for liver transplant. Cells/organs are treated with agonists and antagonists of the mGlu5 receptor. For in vitro experiments, the viability of cells after pharmacological treatment is evaluated by standard techniques, as Trypan Bleu count, MTT colorimetric assay and LDH release. For ex vivo experiments, organ viability is evaluated by means of LDH, AST and ALT release, and organ function by means of bile production. The alteration of gene and protein expression is evaluated, in cell extracts and tissue homogenates, by means of Real Time PCR and Western Blotting.

Recent Publications:

• Ferrigno, A., Vairetti, M., Ambrosi, G., (…), Blandini, F., Fuzzati-Armentero, M.-T. Selective blockade of mGlu5 metabotropic glutamate receptors is protective against hepatic mitochondrial dysfunction in 6-OHDA lesioned Parkinsonian rats. Clinical and Experimental Pharmacology and Physiology 42(6), pp. 695-703
• Ferrigno A, Clarissa Berardo, (…) Mariapia Vairetti. Localization and role of metabotropic glutamate receptors subtype 5 in the gastrointestinal tract. World Journal of Gastroenterology 2017 (accepted for publication, in press).
• Berardo C, L.G. Di Pasqua, (…) Ferrigno A, Vairetti M. Allosteric modulation of mGlu5 receptors by MPEP protects against hepatic cold ischemia and reperfusion injury. 2016, 48:1, e48.

Links:
Scopus author’s page:
https://www.scopus.com/authid/detail.uri?authorId=8870222200
Department author’s page:
http://medint.unipv.eu/site/home/scheda220005649.html