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Alterations in Cortical [ 3 H]Kainate and α‐[ 3 H]Amino‐3‐Hydroxy‐5‐Methyl‐4‐Isoxazolepropionic Acid Binding in a Spontaneous Canine Model of Chronic Hepatic Encephalopathy
Author(s) -
Maddison Jill E.,
Watson Wendy E. J.,
Dodd Peter R.,
Johnston Graham A. R.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb03444.x
Subject(s) - ampa receptor , kainate receptor , hepatic encephalopathy , medicine , glutamate receptor , binding site , endocrinology , chemistry , biology , biochemistry , receptor , cirrhosis
Excitatory amino acid receptor binding parameters were investigated in a spontaneous dog model of chronic hepatic encephalopathy. L‐[ 3 H]Glutamate, (+)‐[ 3 H]‐5‐methyl‐10, 11 ‐dihydro‐5 H ‐dibenzo[ a,d ]cyclohepten‐5, 10‐imine maleate ([ 3 H]MK‐801), [ 3 H]kainate, and α‐[ 3 H]‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid ([ 3 H]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‐[ 3 H]‐glutamate or [ 3 H]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 [ 3 H]kainate binding sites compared with control dogs and abolition of the low‐affinity [ 3 H]AMPA binding site. The relative binding capacity of PSE synaptosomal membranes for [ 3 H]kainate and [ 3 H]AMPA was expressed as the ratio B max / K D . There was a significant inverse correlation between the B max / K D ratio for [ 3 H]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.