Alterations in Cortical [3H]Kainate and α-[3H]Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Binding in a Spontaneous Canine Model of Chronic Hepatic Encephalopathy

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-dibenzoa,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.