EXCITATORY AMINO-ACID RECEPTOR-BINDING IN HIPPOCAMPUS OF GERBILS WITHTRANSIENT GLOBAL BRAIN ISCHEMIA

Binding of a variety of ligands for brain excitatory amino acid recept ors was examined in membrane preparations extensively washed and treat ed with Triton X-100 that were obtained from the hippocampus and cereb ral cortex of gerbils that survived for different periods after transi ent global brain ischemia. Bilateral occlusion of the carotid arteries for 5 min did not affect the binding of ,11-dihydro-5H-di-benzo[a,d]c yclohepten-5,10-imine (MK-801) to an open ion channel associated with the N-methyl-D-aspartate (NMDA)-sensitive subclass in both central str uctures of gerbils that survived for 1 to 4 weeks after the injury whe n determined at equilibrium in the presence of 3 different endogenous agonists including L-glutamic acid (Glu), glycine (Gly) and spermidine at maximally effective concentrations. In contrast, the ischemic occl usion significantly diminished [H-3]MK-801 binding when determined bef ore equilibrium in the presence of the 3 stimulants in hippocampal mem branes without altering that in cortical membranes 2 weeks after the i nsult, so that the initial association rates were invariably reduced b y more than 60%. Moreover, the occlusion not only reduced the binding of both [H-3]Glu and 3]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoi c acid to the NMDA domain on the NMDA receptor ionophore complex, but also decreased the binding of both [H-3]Gly and [H-3]5,7-dichlorokynur enic acid to the Gly domain. However, the insult did not induce any de tectable changes under the experimental conditions employed in either the binding of lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) to the AMPA-sensitive subclass or the binding of kainic acid ( KA) to the KA-sensitive subclass in both central regions of animals th at survived for 2 weeks. These results suggest that transient global b rain ischemia may predominantly impair neuronal and/or glial cells enr iched of the NMDA receptor ionophore complex in gerbil hippocampus.