Mouse hepatocytes lacking mGlu5 metabotropic glutamate receptors are less sensitive to hypoxic damage.

Endogenous activation of type-5 metabotropic glutamate receptors contributes to the development of hypoxia-induced liver cell injury. We have strengthened this hypothesis using glutamate mGlu5 receptor knockout mice. Hepatocytes isolated from knockout mice were less sensitive to hypoxic cell damage than hepatocytes from wild-type mice as assessed by lactate dehydrogenase release and formation of reactive oxygen species. The mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP) also protect hepatocytes against hypoxic damage.