Activation of metabotropic glutamate receptors inhibits synapsin I phosphorylation in visceral sensory neurons

Activation of glutamate metabotropic receptors (mGluRs) in nodose ganglia n eurons has previously been shown to inhibit voltage-gated Ca++ currents and synaptic vesicle exocytosis. The present study describes the effects of mG luRs on depolarization-induced phosphorylation of the synaptic-vesicle-asso ciated protein synapsin I. Depolarization of cultured nodose ganglia neuron s with 60 mM KCI resulted in an increase in synapsin I phosphorylation. App lication of mGluR agonists 1-aminocyclopentane-1s-3r-dicarboxylic acid (t-A CPD) and L(+)-2-Amino-4-phosphonobutyric acid (L-AP4) either in combination or independently inhibited the depolarization induced phosphorylation of s ynapsin I. Application of the mGluR antagonist (RS)-alpha -Methyl-4-carboxy phenylglycine (MCPG) blocked t-ACPD-induced inhibition of synapsin phosphor ylation but not the effects of L-AP4. In addition, application of either t- ACPD or L-AP4 in the absence of KCl induced depolarization had no effect on resting synapsin I phosphorylation. RT-PCR analysis of mGluR subtypes in t hese nodose ganglia neurons revealed that these cells only express group II I mGluR subtypes 7 and 8. These results suggest that activation of mGluRs m odulates depolarization-induced synapsin I phosphorylation via activation o f mGluR7 and/or mGluR8 and that this process may be involved in mGluR inhib ition of synaptic vesicle exocytosis in visceral sensory neurons of the nod ose ganglia.