Non-NMDA glutamate receptor binding in canine brain after global cerebral ischemia and reperfusion.
We employed a canine model to test the effects of global cerebral ischemia and reperfusion on binding to alpha-amino-3-hydroxy-5-methyl- 4-isoxazole proprionate (AMPA), kainate (KA), and metabotropic glutamate receptors. Ischemia was induced by 10 min of cardiac arrest, followed by restoration of spontaneous circulation for periods of 0, 0.5, 2, 4, and 24 h. Frozen sections were prepared from parietal and temporal cortex, hippocampus, and striatum, and in vitro autoradiography was performed with one of three radioligands: [3H]AMPA, [3H]KA, or [3H] glutamate (using conditions allowing specific labeling of the metabotropic binding site). In striatum, metabotropic binding was unchanged, whereas AMPA and KA binding decreased by 20-30% at 30 min postischemia, remaining depressed through 24 h. In cortex, AMPA and metabotropic binding were decreased at several time-points after ischemia and recirculation, particularly in parietal cortex, whereas KA binding was unaffected in this tissue. Binding to hippocampal regions was largely unchanged, except for a decrease in KA binding at 2 and 4 h postischemia. These findings contrast with results from parallel studies showing increased striatal binding to NMDA receptors following ischemia. Decreased binding to non-NMDA glutamate receptors in striatum and parietal cortex may serve to protect against damage mediated through these receptors.
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037, USA.
H
H
Wei
G
G
Fiskum
R E
RE
Rosenthal
D C
DC
Perry
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D016887:Cardiopulmonary Resuscitation; D003342:Corpus Striatum / Q000378:metabolism; D004285:Dogs; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006323:Heart Arrest; D006624:Hippocampus / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007608:Kainic Acid / Q000378:metabolism; D007700:Kinetics; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D010296:Parietal Lobe / Q000378:metabolism; D011869:Radioligand Assay; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015424:Reperfusion; D013702:Temporal Lobe / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D018698:Glutamic Acid; D007608:Kainic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid