Showing papers on "NMDA receptor published in 1974"
TL;DR: Until recently, very little attention has been paid to the possibility of investigating directly the biochemical properties of postsynaptic amino acid receptors, but strychnine, a potent and selective antagonist of glycine-induced hyperpolarisations of spinal neurones, binds specifically to a component of synaptic membranes.
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 antagonists3–6 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 glia9,10 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 transport12–14. 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.
118 citations
TL;DR: A model consisting of a minimum of three compartments seems most compatible with available data and compartment 1, from which glutamine is rapidly formed, is thought to be located in glial cells.
Abstract: THE existence of a compartmented metabolism of glutamate in cerebral cortex is well established1,2 When, for example, glutamate, acetate or γ-aminobutyric acid (GA) are metabolised by the tissue the specific activity of the glutamine formed exceeds that of the total tissue glutamate pool As the immediate precursor of glutamine is glutamate, the implication must be that there is more than one pool of the latter A model consisting of a minimum of three compartments seems most compatible with available data and compartment 1, from which glutamine is rapidly formed, is thought to be located in glial cells1,2
64 citations
TL;DR: There is no information on whether glutamate receptors have the same pharmacological properties as the receptors of the natural excitatory transmitter, and there is also a selective uptake of glutamic acid at the neuromuscular junction which could provide an inactivation mechanism.
Abstract: As Kravitz et al.1 have pointed out, glutamic acid is at present the only candidate for the excitatory transmitter at crustacean neuromuscular junctions. The evidence is that1,2 glutamic acid is the most potent excitatory substance present in the crustacean central nervous system (CNS), whole peripheral nerves and isolated excitatory axons1,3–5; that the glutamic acid content in nerve extracts accounts for the whole of their excitatory activity on crustacean muscles1, and that the receptors to glutamate are localised at the same junctional spots as the receptors to the natural excitatory transmitter6. Also, both glutamic acid and the natural transmitter produce similar changes in the permeability of the postjunctional muscle membrane7–9 and in spite of a large background leakage, a significant release of glutamic acid can be evoked by stimulation of excitatory nerves1. There is also a selective uptake of glutamic acid at the neuromuscular junction which could provide an inactivation mechanism10. There is, however, no information on whether glutamate receptors have the same pharmacological properties as the receptors of the natural excitatory transmitter.
58 citations
TL;DR: “Strong” excitants of central neurones such as β N-oxalyl L α,β-diaminopropionic acid, N-methyl-D-aspartic acid, and kainic acid were found to inhibit the high affinity uptake of glutamate and aspartate in synaptosomes isolated from young rat brain.
34 citations
TL;DR: It is shown that ODAP does not inhibit the glutamate uptake by the high affinity system, which is significant in view of the neurotransmitter function of glutamate, which seems to be neuroexcitory as well as neurotoxic.
Abstract: THE unusual amino acid β-N-oxalyl-L-α, β-diaminopropionic acid (ODAP), isolated from the seeds of Lathyrus sativus is a potent neurotoxin1–3. It produces biochemical changes in the brain typical of an excitant amino acid and is implicated in the aetiology of human neurolathyrism caused by eating the seeds of L. sativus4–6. It may act as a glutamate antagonist: ODAP inhibits glutamate oxidation7 possibly by inhibiting glutamate uptake in bovine brain mitochondria; it also acts as a competitive inhibitor of glutamate uptake in certain strains of yeast8, and a similar process might occur at the synaptic level. Any effect of ODAP on glutamate uptake at synapses is significant in view of the neurotransmitter function of glutamate, which seems to be neuroexcitory as well as neurotoxic9–12. But Balcar and Johnston13 have shown with rat brain slices that ODAP does not inhibit the glutamate uptake by the high affinity system.
31 citations