EXCITATORY AMINO-ACID REGULATION OF ASTROCYTE PROTEOGLYCANS

Activity-dependent enduring change in cellular communication is essent ial for specific connectivity during development of the nervous system and for adaptive responses of the mature nervous system. Here we repo rt that glutamate activation of excitatory amino acid receptors induce s the synthesis and release of proteoglycans (PGs) from fetal hippocam pal astrocytes in dissociated culture. PG synthesis and release are me diated via kainate and metabotropic receptor activation. Glutamate exp osure did not regulate the release of a specific family of PG, but glu tamate inhibited the synthesis of heparan sulfate (HS) PGs that appear ed 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 i ncrease In PG release, However, glutamate-induced PG release was not b locked by inhibition of PKC activity. These data suggest that PKC acti vation can lead to PG release, but is not necessary for it. Activity-d ependent influences on a class of substrate-bound molecular species wi th growth-modulatory properties may be involved in spatial regulation of neuronal growth responses produced by excitatory amino acids.