NMDA receptors and ligands in the vertebrate CNS

Stone, T.W.; Nr, Burton

doi:10.1016/0301-0082(88)90027-5

Cited by 219 publications

(72 citation statements)

References 262 publications

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“…The receptors for the excitatory amino acids have been classified into at least 3 subtypes (N-methyl-Daspartate (NMDA), kainate and quisqualate) as a result of pharmacological investigations (for reviews see Watkins & Evans 1981;McLennan 1983;Stone & Connick 1985;Mayer & Westbrook 1987;Stone & Burton, 1988). Responses involving the activation of the N-methyl-D-aspartate (NMDA) receptor are very sensitive to changes in the extracellular concentration of magnesium (Evans et al, 1977).…”

Section: Introductionmentioning

confidence: 99%

Effect of changing extracellular levels of magnesium on spontaneous activity and glutamate release in the mouse neocortical slice

Smith

Connick

Stone

1989

British J Pharmacology

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1 The mouse neocortical slice preparation, maintained in a two compartment, grease gap bath, exhibits spontaneous depolarizing activity (with or without rhythmic after potentials) after perfusion with magnesium-free artificial cerebrospinal fluid. 2 If the magnesium concentration is decrementally lowered over an extended time period, then incrementally raised following a similar time course, the spontaneous depolarizing shift activity shows a hysteresis (with regard to both frequency and amplitude), the depolarizing shifts being more resistant to magnesium during the the incremental period. 3 The amino acid content of the perfusing fluid was analysed by high performance liquid chromatography (h.p.l.c.). Although a basal efflux of 6 amino acids was quantifiable, only glutamate levels increased following superfusion of the preparation with magnesium-free, artificial cerebrospinal fluid. 4 Glutamate release increased to 266% of the resting release in the presence of magnesium within the first 12min of the change into magnesium-free artificial cerebrospinal fluid. This increase in release preceded the onset of spontaneous depolarising activity. The release of glutamate remained elevated at 182% of control up to 60min after perfusion with magnesium-free buffer, when depolarizing activity was well established. 5 A model is presented and discussed for the genesis and maintenance of the spontaneous depolarizing shifts. It is suggested that the maintenance of this spontaneous activity reflects a long term enhancement of neocortical neurone excitability which may be related to long term potentiation in the hippocampus.

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Section: Introductionmentioning

confidence: 99%

Effect of changing extracellular levels of magnesium on spontaneous activity and glutamate release in the mouse neocortical slice

Smith

Connick

Stone

1989

British J Pharmacology

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“…The early response of human glutamate receptors to such exposure is entirely unknown. Although current experimental evidence on the response of NMDA receptors to chronic stimulation in vivo is equally meager, in vitro data indicate their significant downregulation and reduction of calcium uptake via the NMDA receptor-associated channel (Oster and Schramm, 1993, see also Stone and Burton, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, possible participation of this receptor subtype in other brain disorders (Huntington's and Alzheimer's diseases, epilepsy) has been postulated (Stone and Burton, 1988;Herrling, 1990).…”

Section: Introductionmentioning

confidence: 99%

Chronic NMDA receptor stimulation: therapeutic implications of its effect on adenosine A1 receptors

Lubitz

Kim

Beenhakker

et al. 1995

European Journal of Pharmacology

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It is known that stimulation of adenosine A 1 receptors has a modulatory effect on the excitability of postsynaptic NMDA receptors. Conversely, acute stimulation of NMDA receptors results in release of adenosine via calcium-independent mechanisms. These findings indicate a close functional relationship between these receptors. It is, therefore, possible that chronic, low level stimulation of the NMDA receptor may have a negative impact on these modulatory processes. To investigate this possibility, we have subjected C57BL mice either to an acute injection of a N 6 -cyclopentyladenosine (CPA, 0.01 mg/kg) or deoxycoformycin (1 mg/kg) followed by a convulsant dose of N-methyl-D-aspartate (NMDA) (60 mg/kg) or to chronic, low level (20 mg/kg i.p. daily) exposure to NMDA for 8 weeks. One day after the last injection of NMDA, animals were injected either with a convulsant dose of NMDA alone, or with either CPA at 0.001 or 0.01 mg/kg, or with 1 mg/kg deoxycoformycin followed 15 min later by 60 mg/kg NMDA. Neither CPA nor deoxycoformycin were protective when NMDA was given acutely at 60 mg/kg. Chronic treatment with NMDA alone or chronic administration of NMDA followed by 0.001 mg/kg CPA had no significant effect on mortality following a convulsant dose of NMDA. However, when the chronic regimen of NMDA was followed by either 0.01 mg/kg CPA or 1 mg/kg deoxycoformycin, mortality was reduced to 10% (CPA), or eliminated completely (deoxycoformycin). Moreover, combination of chronic NMDA treatment with either CPA (both doses) or deoxycoformycin produced a significant improvement in other measures, i.e., seizure onset, intensity of neurological impairment, and extension of time to death. Consonant with these results, apparent density of adenosine A 1 receptors was increased in the cortex and hippocampus of animals treated chronically with NMDA. Our results indicate a possible role for NMDA-adenosine A 1 receptor interaction in pathologies in which chronic stimulation of the NMDA receptor by endogenous excitatory amino acids may be involved.

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“…The action of excitatory amino acids is mediated by at least three distinct receptors characterized by the selective agonists N-methyl-D-aspartate (NMDA), quisqualate (QA), and kainate (KA) (for review, see Mayer and Westbrook, 1987;Rothman and Olney, 1987;Stone and Burton, 1988). Biochemical and electrophysiological studies have indicated that each class of receptor plays a distinct role in neu ronal activities (for review, see Mayer and West brook, 1987;Rothman and Olney, 1987;Stone and creased by 44% 7 days after ischemia. Marked loss of the above-mentioned receptors in the CAl after selective de pletion of the CA I pyramidal cells indicated that NMDA receptors, noncompetitive NMDA antagonist binding sites, and KA receptors in the CAl are predominantly localized on the CAl pyramidal cells.…”

mentioning

confidence: 99%

“…Key Words: Cerebral ischemia-Glutamate-Hippocampus Kalinate-NMDA-Phencyclidine. Burton, 1988). Although appropriate activation of NMDA receptors may be beneficial to learning and memory processes, overstimulation of glutamate receptors can lead to neuronal damage (Rothman, 1984;Rothman and Olney, 1987).…”

mentioning

confidence: 99%

Excitatory Amino Acid Binding Sites in the Rat Hippocampus after Transient Forebrain Ischemia

Oda

Araki

Kogure

1989

J Cereb Blood Flow Metab

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The influence of transient forebrain ischemia on the temporal alteration of glutamate receptors in the hippocampal formation was analyzed by means of in vitro quantitative receptor autoradiography. We compared the binding of N-methyl-d-aspartate (NMDA) receptors using [3H]3-((±)2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), noncompetitive NMDA antagonist binding sites using [3H]N-(1-(2-thienyl)-cyclohexyl)-3,4-piperidine (TCP), and kainate (KA) receptors. In the CA1 subfield of the hippocampus, the number of NMDA receptors and noncompetitive NMDA antagonist binding sites remained constant during the early stage of recirculation when the CA1 pyramidal cells remained histologically intact. A significant reduction of these receptor densities was observed 7 days following ischemia, when NMDA receptors and noncompetitive NMDA antagonist binding sites lost 64 and 29% of their binding sites in the stratum radiatum of the CA1, respectively. The KA receptor density in the CA1 subfield decreased by 44% 7 days after ischemia. Marked loss of the above-mentioned receptors in the CA1 after selective depletion of the CA1 pyramidal cells indicated that NMDA receptors, noncompetitive NMDA antagonist binding sites, and KA receptors in the CA1 are predominantly localized on the CA1 pyramidal cells. NMDA receptor density in the CA3 gradually decreased during the recirculation period. The stratum moleculare of the dentate gyrus, whose structure was histologically intact after ischemic insult, also showed a reduction of NMDA receptors 7 days following ischemia. [3H]KA receptor density in the stratum lucidum of the CA3 and in the hilus also decreased during recirculation. These results indicate that postischemic change of neuronal activity was not restricted to the ischemic-lesioned CA1 but that the histologically intact CA3 and dentate gyrus had also modulated neuronal transmission after ischemia.

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NMDA receptors and ligands in the vertebrate CNS

Cited by 219 publications

References 262 publications

Effect of changing extracellular levels of magnesium on spontaneous activity and glutamate release in the mouse neocortical slice

Effect of changing extracellular levels of magnesium on spontaneous activity and glutamate release in the mouse neocortical slice

Chronic NMDA receptor stimulation: therapeutic implications of its effect on adenosine A1 receptors

Excitatory Amino Acid Binding Sites in the Rat Hippocampus after Transient Forebrain Ischemia

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