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

被引:20
作者
Storto, M
Battaglia, G
Gradini, R
Bruno, V
Nicoletti, F
Vairetti, M
机构
[1] Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, I-00185 Rome, Italy
[2] INM Neuromed, Pozzilli, Italy
[3] Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy
[4] Univ Pavia, Dept Internal Med, Pavia, Italy
关键词
mGlu5; knockout; mouse; hypoxia; reactive oxygen species;
D O I
10.1016/j.ejphar.2004.06.023
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:25 / 27
页数:3
相关论文
共 8 条
[1]  
Bergmeyer H.-U., 1965, Methods of Enzymatic Analysis, P736
[2]  
Lu YM, 1997, J NEUROSCI, V17, P5196
[3]  
Moldeus P, 1978, Methods Enzymol, V52, P60
[4]   MOLECULAR DIVERSITY OF GLUTAMATE RECEPTORS AND IMPLICATIONS FOR BRAIN-FUNCTION [J].
NAKANISHI, S .
SCIENCE, 1992, 258 (5082) :597-603
[5]   Pharmacological agents acting at subtypes of metabotropic glutamate receptors [J].
Schoepp, DD ;
Jane, DE ;
Monn, JA .
NEUROPHARMACOLOGY, 1999, 38 (10) :1431-1476
[6]   Selective blockade of mGlu5 metabotropic glutamate receptors protects rat hepatocytes against hypoxic damage [J].
Storto, M ;
de Grazia, U ;
Knöpfel, T ;
Canonico, PL ;
Copani, A ;
Richelmi, P ;
Nicoletti, F ;
Vairetti, M .
HEPATOLOGY, 2000, 31 (03) :649-655
[7]   Selective blockade of mGlu5 metabotropic glutamate receptors is protective against acetaminophen hepatotoxicity in mice [J].
Storto, M ;
Ngomba, RT ;
Battaglia, G ;
Freitas, I ;
Griffini, P ;
Richelmi, P ;
Nicoletti, F ;
Vairetti, M .
JOURNAL OF HEPATOLOGY, 2003, 38 (02) :179-187
[8]   Metabotropic glutamate receptor agonists stimulate polyphosphoinositide hydrolysis in primary cultures of rat hepatocytes [J].
Sureda, F ;
Copani, A ;
Bruno, V ;
Knopfel, T ;
Meltzger, G ;
Nicoletti, F .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 338 (02) :R1-R2