1977884

Presynaptic glutamate/quisqualate receptors: effects on synaptosomal free calcium concentrations.

Article date: 1990/12/1

PubMed ID: 1977884

Journal name: Journal of neurochemistry (ISSN: 0022-3042)

ABSTRACT

Intracellular free [Ca2+]i was measured using fura-2 in synaptosomes prepared from cerebral cortices of adult male rats (12 weeks). L-(+)-Glutamate, D-(-)-glutamate, and quisqualate produced similar dose-dependent increases in [Ca2+]i, with EC50 values of 0.38 microM, 0.74 microM, and 0.1 microM, respectively, and maximum increases of approximately 40%. Ibotenate showed less affinity (EC50 4.4 microM) but had a greater maximum effect (57%). N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) did not increase [Ca2+]i. The increases in [Ca2+]i induced by quisqualate and ibotenate were not diminished in the absence of extrasynaptosomal Ca2+. L-2-Amino-4-phosphonobutyrate (L-AP4) (1 microM) completely blocked the changes in [Ca2+]i induced by L-(+)-glutamate, D-(-)-glutamate, quisqualate, or ibotenate. The effects of quisqualate and ibotenate on [Ca2+]i were also blocked by coincubation of synaptosomes with L-(+)-serine-O-phosphate (L-SP) (1 mM) (which, like L-AP4, blocks the effects of quisqualate and ibotenate on inositol phospholipid metabolism). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) had no effect on agonist-mediated increases in [Ca2+]i when coincubated with either quisqualate or ibotenate. These data are consistent with the existence of presynaptic glutamate receptors (of the excitatory amino acid metabotropic type) which activate phospholipase C leading to the elevation of inositol 1,4,5-trisphosphate and release of Ca2+ from intracellular stores.

Author List: Adamson P, Hajimohammadreza I, Brammer M J, Campbell I C, Meldrum B S

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

Substances mentioned in the article: Aminobutyrates; Excitatory Amino Acid Antagonists; Glutamates; Quinoxalines; Receptors, AMPA; Receptors, Glutamate; Receptors, Neurotransmitter; Phosphoserine; Ibotenic Acid; Glutamic Acid; 6-Cyano-7-nitroquinoxaline-2,3-dione; Quisqualic Acid; 2-amino-4-phosphonobutyric acid; Calcium;

Mesh terms: 6-Cyano-7-nitroquinoxaline-2,3-dione; Aminobutyrates/pharmacology; Animals; Calcium/metabolism; Excitatory Amino Acid Antagonists; Glutamates/metabolism; Glutamic Acid; Ibotenic Acid/antagonists & inhibitors; Male; Phosphoserine/pharmacology; Quinoxalines/pharmacology; Quisqualic Acid/antagonists & inhibitors; Rats; Rats, Inbred Strains; Receptors, AMPA; Receptors, Glutamate; Receptors, Neurotransmitter/metabolism; Synapses/metabolism; Synaptosomes/metabolism;

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