Rats With Different Thresholds to Clonic Convulsions Induced by DMCM Differ in the Binding of [H-3]-MK-801 and [H-3]-Ouabain in the Membranes of Brain Regions
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2012-07-01
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Considering the putative participation of N-methyl-D-aspartate (NMDA) receptors and the Na+, K+-ATPase enzymes in the susceptibility to convulsions induced by the benzodiazepine inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), the present study sought to determine if rats with high (HTR) and low (LTR) thresholds to clonic convulsions induced by DMCM differed in the following aspects: the binding of NMDA receptors by [H-3]-MK-801, Na+, K+-ATPase activity (K+-stimulated p-nitrophenylphosphatase) and high-affinity [H-3]-ouabain binding to membranes from discrete brain regions. Compared to the HTR subgroup, the LTR subgroup presented a lower binding of [H-3]-MK-801 in the hippocampus, frontal cortex and striatum. the subgroups did not differ in K+-p-nitrophenylphosphatase activity, but the LTR subgroup had a lower density of isozymes with a high-affinity to ouabain in the brainstem and in the frontal cortex and a lower affinity to ouabain in the hippocampus than the HTR subgroup. These results suggest that NMDA receptors and ouabain-sensitive Na+, K+-ATPase isozymes may underlie the susceptibility to DMCM-induced convulsions.
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Neurochemical Research. New York: Springer/plenum Publishers, v. 37, n. 7, p. 1442-1449, 2012.