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Excitatory amino acid receptor binding in hippocampus of gerbils with transient global brain ischemia
Abstract:
Binding of a variety of ligands for brain excitatory amino acid receptors was examined in membrane preparations extensively washed and treated with Triton X-100 that were obtained from the hippocampus and cerebral cortex of gerbils that survived for different periods after transient global brain ischemia. Bilateral occlusion of the carotid arteries for 5 min did not affect the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to an open ion channel associated with the N-methyl-D-aspartate (NMDA)-sensitive subclass in both central structures of gerbils that survived for 1 to 4 weeks after the injury when 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 occlusion significantly diminished [3H]MK-801 binding when determined before equilibrium in the presence of the 3 stimulants in hippocampal membranes without altering that in cortical membrane 2 weeks after the insult, so that the initial association rates were invariably reduced by more than 60%. Moreover, the occlusion not only reduced the binding of both [3H]Glu and [3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid to the NMDA domain on the NMDA receptor ionophore complex, but also decreased the binding of both [3H]Gly and [3H]5,7-dichlorokynurenic acid to the Gly domain. However, the insult did not induce any detectable changes under the experimental conditions employed in either the binding of [3H]DL-alpha-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 that survived for 2 weeks. These results suggest that transient global brain ischemia may predominantly impair neuronal and/or glial cells enriched of the NMDA receptor ionophore complex in gerbil hippocampus.