Alterations in cortical [3H]kainate and alpha-[3H]amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding in a spontaneous canine model of chronic hepatic encephalopathy.

Article date: 1991/6/1

PubMed ID: 1673994

Journal name: Journal of neurochemistry (ISSN: 0022-3042)


Excitatory amino acid receptor binding parameters were investigated in a spontaneous dog model of chronic hepatic encephalopathy. L-[3H]Glutamate, (+)-[3H]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-im ine maleate ([3H]MK-801), [3H]kainate, and alpha-[3H]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) binding experiments were performed using crude cerebrocortical synaptosomal membrane preparations from dogs with congenital portosystemic encephalopathy (PSE) and control dogs. There was no change in the affinity or density of L-[3H]-glutamate or [3H]MK-801 binding sites in dogs with congenital PSE compared with control dogs. However, in the PSE dogs there was a significant reduction in the density of [3H]kainate binding sites compared with control dogs and abolition of the low-affinity [3H]AMPA binding site. The relative binding capacity of PSE synaptosomal membranes for [3H]kainate and [3H]AMPA was expressed as the ratio Bmax/KD. There was a significant inverse correlation between the Bmax/KD ratio for [3H]AMPA binding and the worst grade of encephalopathy experienced by each dog. These results suggest that there is a significant perturbation of cerebrocortical non-N-methyl-D-aspartate receptor binding in dogs with congenital PSE which may have relevance to the pathogenesis of hepatic encephalopathy.

Author List: Maddison J E, Watson W E, Dodd P R, Johnston G A

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Glutamates; Ligands; Tritium; Ibotenic Acid; Glutamic Acid; Dizocilpine Maleate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Kainic Acid;

Mesh terms: Animals; Cerebral Cortex/metabolism; Chronic Disease; Dizocilpine Maleate/metabolism; Dogs; Glutamates/metabolism; Glutamic Acid; Hepatic Encephalopathy/metabolism; Ibotenic Acid/analogs & derivatives; Kainic Acid/metabolism; Ligands; Tritium; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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