Metabotropic receptors and 'slow' excitatory actions of glutamate agonists in the hippocampus.

The actions of glutamate in the CNS can be divided into ionotropic and metabotropic effects. The ionotropic receptors participate in synaptic transmission by directly opening nonselective cation channels. Recently, a so-called 'metabotropic effect' of glutamate has been described and is attributed to a novel metabotropic glutamate receptor. This effect consists of increased hydrolysis of membrane phosphoinositides, production of the second messengers diacylglycerol and inositol 1,4,5-trisphosphate, and mobilization of intracellular Ca2+. Activation of metabotropic glutamate receptors blocks the slow Ca(2+)-dependent K+ conductance and increases the membrane excitability of neurones. In addition, metabotropic agonists block the excitatory synaptic transmission supported by the ionotropic glutamate receptor, and may therefore play a critical role in synaptic plasticity. However, intracellular mechanisms linking metabotropic glutamate receptors with ionic channels remain unclear. This article discusses recent findings concerning metabotropic agonist effects on membrane currents and synaptic transmission, the pharmacology of the agonists and the roles played by G proteins and second messengers in mediating their effects.