Glutamate receptors in the rat central nervous system

Abstract

ALTHOUGH it is widely accepted that glutamate may be a significant central transmitter (for reviews, see refs 1 and 2), definitive neuropharmacological evidence at the synaptic level has not been forthcoming, and studies with proposed glutamate antagonists^3–6 have yielded anomalous results. On the basis of biochemical evidence, however⁷, glutamate fulfils many of the criteria expected of a neurotransmitter; in particular, nerve endings⁸ and glia^9,10 possess high-affinity transport systems for glutamate, which it is thought, in common with other amino acid neurotransmitters, are responsible for terminating its synaptic actions. For these high-affinity systems to function, there is a stringent requirement for sodium¹¹, which may be involved in the initial binding phase at the reuptake site, prior to transport^12–14. Until recently, very little attention has been paid to the possibility of investigating directly the biochemical properties of postsynaptic amino acid receptors. Young and Snyder¹⁵ have demonstrated that strychnine, a potent and selective antagonist of glycine-induced hyperpolarisations of spinal neurones, binds specifically to a component of synaptic membranes; this is probably the physiological glycine receptor since strychnine has negligible affinity for the glycine high-affinity uptake system. The specific γ-aminobutyric acid (GABA) antagonist, bicuculline, has also been found to competitively inhibit GABA binding to synaptosomes, in which the uptake site had been inactivated by chlorpromazine¹⁶. In both these cases, binding to the postsynaptic receptor was not affected by the absence of sodium.