Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

Abstract

Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate (NMDA) receptor population on brain homogenates in rabbits was studied during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Homogenates were prepared from brain cortex, hippocampus and striatum. Hepatic encephalopathy was induced by a two-stage liver devascularization procedure and acute hyperammonemia by a prolonged ammonium-acetate infusion; rabbits receiving a sodium-potassium-acetate infusion served as controls. In these animal models extracellular brain glutamate levels are known to be elevated. However no significant alterations in the number nor the affinity of the MK-801 binding sites of the NMDA receptors were found during acute liver failure and acute hyperammonemia. These findings suggest that the NMDA receptor population remains unaltered in experimental encephalopathy from acute liver failure and acute hyperammonemia, despite alterations in extracellular brain glutamate levels.KEYWORDS: hepatic encephalopathy; ammonia; glutamate receptors; NMDAreceptors; MK-801. Abbreviations used in the text: NMDA_N-methyl-D-aspar tate; NH4Ac ammoniumacetate;NaKAc sodium/potassium-acetate; AMPA amino -3 -hydroxy-5 -methylisoxazole-4-propionic acid

Selective Loss of Binding Sites for the Glutamate Receptor Ligands [3H]Kainate and (S)–[3H]5–Fluorowillardiine in the Brains of Rats With Acute Liver Failure

“…24 The results of the present study confirm and extend these findings. On the other hand, both the present and previous studies 7,25 show no significant alterations in binding-site densities for the NMDA-receptor ligand [ 3 H]MK801, suggesting that this predominantly neuronal subclass of glutamate receptor is not modified in acute liver failure.…”

The brain glutamate system in liver failure

“…Decreased densities of binding sites for ligands of AMPA/ kainate receptors were reported in the brains of rats with ALF induced by hepatic devascularization . In contrast, densities of NMDA receptor ligands were shown to be unchanged in this model (Michalak et al 1996) as well as in brain preparations from rabbits with ALF or acute hyperammonemia (de Knegt et al 1993). Subsequent evidence that both neurons and astrocytes may express similar subclasses of glutamate receptors (Carmignoto 2000), however, hampers the interpretation of these findings.…”

“…In contrast, densities of NMDA receptor ligands were shown to be unchanged in this model (Michalak et al . 1996) as well as in brain preparations from rabbits with ALF or acute hyperammonemia (de Knegt et al . 1993).…”

Untitled

“…Similar findings of a significant loss of [ 3 H]-kainate binding sites were subsequently reported in frontal cortex in ischemic liver failure in the rat . In contrast, densities of neuronally localized NMDA binding sites are unchanged in ischemic liver failure in both rabbits (de Knegt et al, 1993) and rats (Michalak et al, 1996). Furthermore, a selective loss of AMPA receptor binding sites was found in the brains of rats with ischemic liver failure .…”