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.
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.
Department of Pharmacology, University of Sydney, New South Wales, Australia.
J E
JE
Maddison
W E
WE
Watson
P R
PR
Dodd
G A
GA
Johnston
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002908:Chronic Disease; D016291:Dizocilpine Maleate / Q000378:metabolism; D004285:Dogs; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism*; D008024:Ligands; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D008024:Ligands; D014316:Tritium; D007051:Ibotenic Acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid