Heterologous mammalian expression systems for investigating the properties of metabotropic glutamate receptors.

Abstract

Introduction The amino acid ],-glutamate is the principal excitatory neurotransmitter in the central nervous system. Through its interaction with a broad variety of receptors present at the surface of responding cells, 1.-glutamate has been proposed to be involved in learning activity and memory acquisition, but also in neurotoxicity and diverse neurological disorders. Distinct families of glutamate receptors have been identified and these are either directly coupled to changes in cation conductance (ionotropic receptors) or to GTP-binding proteins (metabotropic receptors) (reviewed in [ 11). Ionotropic glutamate receptors (iGlu receptors) are involved in triggering the immediate actions of released glutamate at the postsynaptic neuron. Metabotropic glutamate (mGlu) receptors are involved in the control of glutamatergic neurotransmission through the modulation of glutamate release at a presynaptic level and its actions at a postsynaptic level, and therefore have been proposed to have important regulatory roles in synaptic plasticity and neuronal excitability [l]. In the central nervous system, the nature of glutamate transmission is dependent on the combinations of these different subtypes of receptors at the synapse [2]. Although the physiological activities of mGlu receptors seem to be restricted to the central nervous system, a substantial proportion of the information currently accruing on mGlu receptor function is derived from experiments performed in heterologous expression systems, which often utilize non-neuronal mammalian cell models. This review provides an overview of the informa-