Excitatory amino acid regulation of astrocyte proteoglycans

Activity-dependent enduring change in cellular communication is essential for specific connectivity during development of the nervous system and for adaptive responses of the mature nervous system. Here we report that glutamate activation of excitatory amino acid receptors induces the synthesis and release of proteoglycans (PGs) from fetal hippocampal-astrocytes in dissociated culture. PG synthesis and release are mediated via kainate and metabotropic receptor activation. Glutamate exposure did not regulate the release of a specific family of PG, but glutamate inhibited the synthesis of heparan sulfate (HS) PGs that appeared within the extracellular environment of the astrocyte. Particulate protein kinase C (PKC) activity was increased by glutamate and the PKC activator phorbol 10-myristate 13-acetate produced a dose-dependent increase in PG release. However, glutamate-induced PG release was not blocked by inhibition of PKC activity. These data suggest that PKC activation can lead to PG release, but is not necessary for it. Activity-dependent influences on a class of substrate-bound molecular species with growth-modulatory properties may be involved in spatial regulation of neuronal growth responses produced by excitatory amino acids.