Neuroprotection by group I metabotropic glutamate receptor antagonists in forebrain ischemia of gerbil.
Stimulation of group I metabotropic glutamate receptors (mGluR 1 and 5) activates G-protein coupled-phospholipase C (PLC) to release 1,2-diacylglycerol (DAG) and arachidonic acid (ArAc). To elucidate the role of group I mGluR, we tested the effects of (S)-alpha-methyl-4-carboxy-phenylglycine (MCPG, mGluR 1 and 5 antagonist), 1-aminoindan-1,5-dicarboxylic acid (AIDA, mGluR 1a specific antagonist) and 2-methyl-6-(phenylethynyl) pyridine (MPEP, mGluR 5 antagonist) on ArAc release and neuronal survival after transient forebrain ischemia in gerbils. Ischemia resulted in (a) significant release of ArAc at 1-day reperfusion and (b) significant neuronal death in the hippocampal CA1 subfield after 6-day reperfusion. MCPG and MPEP decreased ArAc release and also significantly increased neuronal survival. AIDA was less effective in decreasing ArAc release and had no effect on neuronal death. These results suggest that activation of mGluR 5 may be an important pathway in ArAc release and neuronal death after transient ischemia.
Rao
A M
AM
Department of Neurological Surgery, Clinical Science Center, University of Wisconsin, Veterans Administration Hospital, Madison 53792, USA. adibhatl@neurosurg.wisc.edu
Hatcher
J F
JF
Dempsey
R J
RJ
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D001565:Benzoates / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005849:Gerbillinae; D005998:Glycine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016548:Prosencephalon / Q000098:blood supply*; D011725:Pyridines / Q000627:therapeutic use*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
C095756:1-aminoindan-1,5-dicarboxylic acid; D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018696:Neuroprotective Agents; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C079694:alpha-methyl-4-carboxyphenylglycine; D016718:Arachidonic Acid; C121465:6-methyl-2-(phenylethynyl)pyridine; D005998:Glycine