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Group I metabotropic glutamate receptors (group I mGluRs; mGluR1 and mGluR5) exert diverse effects on neuronal and synaptic functions, many of which are regulated by intracellular Ca 2+ . In this study, we characterized the cellular mechanisms underlying Ca 2+  mobilization induced by ( RS )-3,5-dihydroxyphenylglycine (DHPG; a specific group I mGluR agonist) in the somata of acutely dissociated rat hippocampal neurons using microfluorometry. We found that DHPG activates mGluR5 to mobilize intracellular Ca 2+  from ryanodine-sensitive stores via cyclic adenosine diphosphate ribose (cADPR), while the PLC/IP 3  signaling pathway was not involved in Ca 2+  mobilization. The application of glutamate, which depolarized the membrane potential by 28.5±4.9 mV (n = 4), led to transient Ca 2+  mobilization by mGluR5 and Ca 2+  influx through L-type Ca 2+  channels. We found no evidence that mGluR5-mediated Ca 2+  release and Ca 2+  influx through L-type Ca 2+  channels interact to generate supralinear Ca 2+  transients. Our study provides novel insights into the mechanisms of intracellular Ca 2+  mobilization by mGluR5 in the somata of hippocampal neurons.

Cyclic ADP Ribose-Dependent Ca2+ Release by Group I Metabotropic Glutamate Receptors in Acutely Dissociated Rat Hippocampal Neurons