The Human Brain : From Neurone to Nervous System
SYNAPSES : METABOTROPIC RECEPTORS
Metabotropic receptors act on signal transduction mechanisms within the neurone, which in turn influence the activity of ion channels and other cellular functions including gene expression
Glutamate metabotropic receptors (mGluRs) act on membrane G-proteins that influence signal transduction mechanisms within the neurone, such as :
- the phosphatidylinositol signalling pathway (Group I mGluRs)
- the cAMP signal pathway (Groups II and III mGluRs)
- Binding of glutamate with Group 1 mGluRs causes the enzyme phospholipase C to hydrolyze phosphoinositides to inositol trisphosphate (IP3) and diacyl glycerol (DAG). These mediators initiate the insertion of additional NMDA receptors into the post-synaptic membrane, which can increase levels of intracellular calcium concentrations to toxic levels when these channels are open.
Binding of glutamate with Group II and III receptors prevents the formation of cyclic adenosine monophosphate (cAMP) and reduces the activity of post-synaptic NMDA receptors. The decreased activity is due to the internalisation of some NMDA receptors from the membrane. Their action is therefore regarded as neuroprotective against the excitotoxic actions of glutamate. This group are also involved in presynaptic inhibition.
Overall, the glutamate metabotropic receptors are involved in synaptic plasticity, neurotoxicity and neuroprotection, long term potentiation and long term depression; theiy achieve these functions largely by changing the expression of post-synaptic activity of NMDA receptors, or by their involvement in presynaptic inhibition.
Key Words: Glutamatergic metabotropic receptors, regulation of NMDA receptor expression; pre-synaptic inhibition; neurotoxicity, neuroprotection.