Presynaptic glutamate/quisqualate receptors: effects on synaptosomal free calcium concentrations.
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.
Adamson
P
P
Department of Neuroscience, Institute of Psychiatry, London, England.
Hajimohammadreza
I
I
Brammer
M J
MJ
Campbell
I C
IC
Meldrum
B S
BS
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D010768:Phosphoserine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D000613:Aminobutyrates; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D010768:Phosphoserine; D007051:Ibotenic Acid; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016318:Quisqualic Acid; C012729:2-amino-4-phosphonobutyric acid; D002118:Calcium