Presynaptic Glutamate/Quisqualate Receptors: Effects on Synaptosomal Free Calcium Concentrations

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Abstract
Intracellular free [Ca2+]j 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 μM, 0.74 μM, and 0.1 μM, respectively, and maximum increases of approximately 40%. Ibotenate showed less affinity (EC50 4.4 μM) but had a greater maximum effect (57%). N‐methyl‐d‐aspartate (NMDA) and α‐ 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 μM) 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.