Cultured neurons as model systems for biochemical and pharmacological studies on receptors for neurotransmitter amino acids.

By the use of primary cultures of neurons consisting of cerebral cortex interneurons or cerebellar granule cells it is possible to study biochemical and pharmacological aspects of receptors for GABA and glutamate. Cerebellar granule cells have been shown to express both high- and low-affinity GABA receptors. The latter ones develop, however, only when the neurons are treated with GABA or GABA receptor agonists. It is suggested that the high-affinity receptors play a role in the neurotrophic activity of GABA, whereas the low-affinity GABA receptors are involved in the mediation of the inhibitory action of GABA on evoked release of glutamate, which is the neurotransmitter in cerebellar granule cells. Also glutamate receptors have been studied with regard to the 2 types of neurons. Both cerebral cortex neurons (GABAergic) and cerebellar granule cells (glutamatergic) possess glutamate receptors, which mediate an L-glutamate-induced transmitter release. The pharmacological properties of these glutamate receptors are, however, distinctly different for the 2 types of neurons. While cerebral cortex neurons express both quisqualate-, N-methyl-D-aspartate- and kainate-receptors, the cerebellar granule cells have a receptor which is activated only by L-glutamate and L-aspartate.