Metabotropic glutamate receptors trigger postsynaptic protein synthesis.

K+ depolarization or addition of glutamate to a synaptoneurosome preparation triggers a rapid increase in size of polyribosomal aggregates isolated by centrifugation of lysate through 1 M sucrose. The profile of response to the glutamate analogues quisqualate, ibotenate, and 1-aminocyclopentane-1,3-dicarboxylate corresponds to that of metabotropic receptors. Glutamate stimulation is mimicked by the diacylglycerol analogue 1-oleoyl-2-acetylglycerol and by the protein kinase C activator phorbol dibutyrate. The phospholipase blockers 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate and quinacrine reduce the late phase of the response. The protein kinase C inhibitor calphostin C suppresses the response to 1-aminocyclopentane-1,3-dicarboxylate. These data indicate that glutamatergic synapses upregulate postsynaptic protein synthesis via metabotropic glutamate receptors coupled to the phosphatidylinositol second-messenger system. This mechanism could underlie the reported involvement of metabotropic glutamate receptors in long-term potentiation and other forms of neural plasticity.