EXCITATORY AMINO-ACID-INDUCED, EXCEPT 1S,3R-ACPD, INDUCED TRANSIENT HIGH STIMULATION OF PHOSPHOINOSITIDE METABOLISM DURING HIPPOCAMPAL NEURON DEVELOPMENT

Rat hippocampal neurons in culture extended their neurites until day 5 in vitro (DIV). Then, the mean neuritic length slightly decreased. Ex citatory amino acid (EAA)-elicited inositol phosphate (IF) formation i ncreased from 0.5 to 2 DIV, reached a plateau between 2 and 4-5 DIV, a nd then gradually decreased until 10 DIV. This decrease was likely not due to neuronal death. This developmental pattern was observed for N- methyl-D-aspartate, kainate, glutamate, ibotenate and quisqualate (QA) . Interestingly, the 1S,3R-aminocyclopentane dicarboxylate (1S,3R-ACPD ) response slightly increased during neuronal culture development. At 3 DIV, the ionotropic antagonists 6,7-dinitro-quinoxalin-2,3-dion and D-2-amino-5-phosphonopentanoate efficiently blocked N-methyl-D-asparta te and kainate-elicited IP formation, and partially inhibited glutamat e and ibotenate responses. QA and 1S,3R-ACPD responses were not affect ed, suggesting a metabotropic action for these two compounds. Furtherm ore, QA and 1S,3R-ACPD potencies significantly increased between 3 and 10 DIV. The transient high activity periods induced by EAA, except fo r 1S,3R-ACPD, are not observed for norepinephrine, carbachol and potas sium chloride responses. Taken together, these data suggest that: (i) QA and 1S,3R-ACPD can act on two different glutamate metabotropic rece ptors subtypes during development; and (ii) the EAA-induced transient peaks of IP stimulation, which are specific with respect to other neur oactive substances profiles, could be involved in the development of h ippocampal neurons. Indeed, these transient high activities take place when the neuritic length regularly increases in vitro.