Article date: 1991/11/15
PubMed ID: 1657970
Journal name: The Journal of biological chemistry (ISSN: 0021-9258)
The venom of the North American funnel-web spider Agelenopsis aperta contains a variety of arylamine toxins (the alpha-agatoxins) that paralyze insects by blocking glutamatergic neuromuscular transmission. We have tested six synthetic alpha-agatoxins for their ability to antagonize glutamate receptor function in mammalian brain. These compounds produce, at submicromolar concentrations, noncompetitive inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated elevations in the concentration of cytosolic free calcium in cultured rat cerebellar granule neurons. In contrast, the alpha-agatoxins are relatively weak antagonists of elevations in the cytosolic free calcium concentration induced by non-NMDA receptor agonists. The alpha-agatoxins also produce reversible suppression of the NMDA receptor-mediated excitatory postsynaptic potential in rat hippocampal slices at concentrations that have little effect on the non-NMDA receptor-mediated population spike. We conclude that the alpha-agatoxins are selective and reversible noncompetitive antagonists at NMDA receptors in mammalian brain.
Author List: Parks T N, Mueller A L, Artman L D, Albensi B C, Nemeth E F, Jackson H, Jasys V J, Saccomano N A, Volkmann R A
Publication Types: Journal Article
Substances mentioned in the article: Receptors, N-Methyl-D-Aspartate; Spider Venoms; Ibotenic Acid; N-Methylaspartate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Kainic Acid; Calcium; Glycine;
Mesh terms: Animals; Brain/drug effects; Calcium/metabolism; Cells, Cultured; Cerebellum/metabolism; Cytosol/metabolism; Evoked Potentials/drug effects; Glycine/pharmacology; Hippocampus/drug effects; Ibotenic Acid/analogs & derivatives; In Vitro Techniques; Kainic Acid/pharmacology; Kinetics; N-Methylaspartate/pharmacology; Neurons/drug effects; Rats; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors; Spider Venoms/pharmacology; Structure-Activity Relationship; Synapses/drug effects; Synaptic Transmission/drug effects; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;