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: Marcos Brandão Contó, José Gilberto Barbosa de Carvalho, Marco Antonio Campana Venditti
• Journal: Neurochemical research (Neurochem Res) Vol. 37 Issue 7 Pg. 1442-9 (Jul 2012) ISSN: 1573-6903 [Electronic] United States
• PMID: 22382813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbolines
• Tritium
• methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate
• Ouabain
• Dizocilpine Maleate

Topics

• Animals
• Brain (metabolism)
• Carbolines (toxicity)
• Dizocilpine Maleate (metabolism)
• Male
• Ouabain (metabolism)
• Radioligand Assay
• Rats
• Rats, Wistar
• Seizures (chemically induced)
• Tritium