title: Rats with different thresholds to clonic convulsions induced by DMCM differ in the binding of [3H]-MK-801 and [3H]-ouabain in the membranes of brain regions.
abstract: 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-β-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 [(3)H]-MK-801, Na(+), K(+)-ATPase activity (K(+)-stimulated p-nitrophenylphosphatase) and high-affinity [(3)H]-ouabain binding to membranes from discrete brain regions. Compared to the HTR subgroup, the LTR subgroup presented a lower binding of [(3)H]-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.
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/EPM), Rua Botucatu 862, 1° andar, Vila Clementino, São Paulo, SP, 04023-062, Brazil. mmmarcos@uol.com.br
authors.forename: Marcos Brandão
authors.initials: MB
authors.lastname: Contó
authors.forename: José Gilberto Barbosa
authors.initials: JG
authors.lastname: de Carvalho
authors.forename: Marco Antonio Campana
authors.initials: MA
authors.lastname: Venditti
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*; D014316:Tritium
chemical_list: D002243:Carbolines; D014316:Tritium; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D010042:Ouabain; D016291:Dizocilpine Maleate