Article date: 1991/9/16
PubMed ID: 1686641
Journal name: Neuroscience letters (ISSN: 0304-3940)
Binding of glutamate and muscimol (an agonist for GABAA receptors) to their respective receptors has been studied in the cerebellum of normal and hyperammonemic rats. There was a decrease in both high- and low-affinity binding of glutamate in the cerebellum during hyperammonemia. Kinetic studies revealed that the decrease is due to a reduction in the number of binding sites, but not due to changes in the binding affinities. Further studies also revealed that the decrease was only in the N-methyl-D-aspartate (NMDA)-specific binding sites without any alterations in the binding to non-NMDA sites represented by kianic acid (KA)- and quisqualic acid (QQ)-sensitive receptor sites. These effects were also mimicked when the membrane preparations from the cerebellum of normal animals were incubated with ammonium acetate. Enhancement of muscimol binding was observed in animals injected with ammonium acetate. It is concluded that hyperammonemic states, even in the presence of a functional liver, are capable of altering amino acid neurotransmission and this might play an important role in cerebral dysfunction under these conditions.
Author List: Rao V L, Agrawal A K, Murthy C R
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Glutamates; Receptors, GABA-A; Receptors, Glutamate; Receptors, Neurotransmitter; Muscimol; Glutamic Acid; N-Methylaspartate; Ammonia; Quisqualic Acid; Kainic Acid;
Mesh terms: Ammonia/blood; Animals; Cerebellum/metabolism; Glutamates/metabolism; Glutamic Acid; Kainic Acid/pharmacology; Kinetics; Muscimol/metabolism; N-Methylaspartate/pharmacology; Quisqualic Acid/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/metabolism; Receptors, Glutamate; Receptors, Neurotransmitter/metabolism; Synaptic Membranes/metabolism;