A double inhibition kinetic analysis of [3H]-muscimol binding to the gamma-aminobutyric acid receptor on calf brain synaptic membranes. Further studies on the mechanism of homocysteine-induced seizures.

Article date: 1985/10/1

PubMed ID: 2996552

Journal name: Biochemical pharmacology (ISSN: 0006-2952)


The simultaneous action of pyridoxal 5'-phosphate (PLP) and L-homocysteine on specific [3H]muscimol binding to the gamma-aminobutyric acid receptor on freeze-thawed, Triton-treated calf-brain synaptic membranes was examined kinetically by double inhibition analysis. PLP was found to be a pure inhibitor and L-homocysteine, a partial inhibitor, with respect to [3H]muscimol. Diagnostic analysis of the experimental data showed that the interaction constant (alpha) of the two inhibitors for the free receptor is between 0 and 1, confirming that the two inhibitors act synergistically. Further double inhibition analysis showed that no quaternary receptor-[3H]muscimol-homocysteine-PLP complex is formed although the ternary receptor-homocysteine-PLP complex is present. The localization and relationship of binding groups for both inhibitors is discussed as in their association with the ligand binding site.

Author List: Griffiths R, Egbuta J O

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Macromolecular Substances; Receptors, GABA-A; Homocysteine; Muscimol; Pyridoxal Phosphate;

Mesh terms: Animals; Binding, Competitive; Brain/metabolism; Cattle; Drug Synergism; Homocysteine/metabolism; Kinetics; Macromolecular Substances; Muscimol/metabolism; Pyridoxal Phosphate/metabolism; Receptors, GABA-A/drug effects; Seizures/chemically induced; Synaptic Membranes/metabolism;

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