Excitatory Amino Acid-Induced Formation of Inositol Phosphates in Guinea-Pig Cerebral Cortical Slices: Involvement of Ionotropic or Metabotropic Receptors?

Abstract

In cerebral cortical slices from the guinea‐pig, quinoxalinedione derivatives antagonised the generation of ³H‐inositol phosphates evoked by the excitatory amino acids quisqualate and DL‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxalone propionic acid but were without effect on the trans‐DL‐1‐amino‐ 1,3‐cyclopentanedicarboxylic acid and l‐glutamate responses. Omission of calcium from the medium reduced the accumulation of ³H‐inositol phosphates induced by incubation with trans‐DL‐1‐amino‐ 1,3‐cyclopentanedicarboxylic acid (incubation for 45 min) by > 50%, whereas the responses to l‐glutamate and the two other amino acid analogues were reduced by ∼20%. Generation of inositol 1,4,5‐trisphosphate over a 30‐s period by treatment with quisqualate, trans‐DL‐1‐amino‐ 1,3‐cyclopentanedicarboxylic acid, KCI, and carbachol was abolished in the presence of nominally calcium‐free medium. l‐Glutamate induced a large, rapid increase in inositol 1,4,5‐trisphosphate mass (more than threefold), which was, however, unaffected by omission of calcium from the medium. These results indicate that of the excitatory amino acids tested, only l‐glutamate may be classed as a metabotropic receptor agonist in guinea‐pig cerebral cortical slices with respect to generation of inositol phosphates. The other agents appear to stimulate accumulation of inositol phosphates, at least in part through some mechanism requiring the presence of extracellular Ca²⁺, presumably Ca²⁺ entry.