Pharmacological heterogeneity of NMDA receptors in cerebellar granule cells in immature rat slices. A microfluorimetric study with the [Ca2+]i sensitive dye indo-1

Perrier, M.L.; Bénavidès, J.

doi:10.1016/0028-3908(94)00130-k

Cited by 14 publications

(5 citation statements)

References 27 publications

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“…In contrast to synapses in the thalamus, neocortex, brainstem and hippocampus (Salt, 1989; Thomson et al ., 1989; Berger et al ., 1998; Bergeron et al ., 1998; Chen et al ., 2003), adding glycine or d ‐serine to the extracellular solution had no effect on the size of the NMDA component of the EPSC at the mossy fibre to granule cell synapse (Fig. 1), as found previously for NMDA‐evoked [Ca 2+ ] i rises in granule cells (Perrier & Benavides, 1995). Thus, the main conclusion of our paper is that the glycine site on these NMDA receptors is saturated.…”

Section: Discussionsupporting

confidence: 83%

Active release of glycine or d‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse

Billups

Attwell

2003

Eur J of Neuroscience

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The current and calcium influx generated by NMDA receptors depend on the concentration of the coagonist glycine, or its analogue d-serine, in the synaptic cleft. If there is no release of glycine, the ionic stoichiometry of the glial GlyT1 glycine transporters expressed near NMDA receptors in the brain should be able to lower the extracellular glycine concentration to below the EC50 for coactivation of NMDA receptors. We examined whether changing the glycine or d-serine concentration in the superfusion solution altered the NMDA receptor mediated component of the synaptic current at the rat cerebellar mossy fibre to granule cell synapse. Adding up to 100 microM glycine or d-serine had no effect, implying that the glycine site is saturated. Using the competitive glycine site antagonist 7-chlorokynurenate, and plausible values for the kinetic parameters of NMDA receptors, we estimate that during activation of the mossy fibres the concentration of glycine or d-serine in the synaptic cleft is at least 4.6 microM or 1.5 microM, respectively, requiring active release of glycine or d-serine.

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Section: Discussionsupporting

confidence: 83%

Active release of glycine or d‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse

Billups

Attwell

2003

Eur J of Neuroscience

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“…However, the inhibition curves for both of these antagonists were substantially shifted to the right compared with the corresponding ligand binding curves. A similarly high IC 50 for MK-801 inhibition of NMDA receptor-mediated increases in intracellular calcium in cerebellar granule cells has been reported (73). This pharmacological profile matches that seen for inhibition of glutamate-induced cell death in transfected HEK 293 cells as the IC 50 for MK-801 inhibition of cell death in NR 1/2A-transfected cells is similarly high (0.795 M; Ref.…”

Section: Discussionsupporting

confidence: 67%

N-Methyl-D-aspartate Receptors Expressed in a Nonneuronal Cell Line Mediate Subunit-specific Increases in Free Intracellular Calcium

Grant

Bacskai

Pleasure

et al. 1997

Journal of Biological Chemistry

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N-methyl-D-aspartate (NMDA) receptors can mediate cell death in neurons and in non-neuronal cells that express recombinant NMDA receptors. In neurons, increases in intracellular calcium correlate with NMDA receptor-mediated death, supporting a key role for loss of cellular calcium homeostasis in excitotoxic cell death. In the present study, free intracellular calcium concentrations were examined in response to activation of recombinant NMDA receptors expressed in human embryonic kidney 293 cells. Intracellular calcium was measured in transfected cell populations by cotransfection with the calcium-sensitive, bioluminescent protein aequorin and by single cell imaging with the fluorescent calcium indicator fluo-3. Agonist application to NR1/2A or NR1/2B-transfected cells elicited robust rises in intracellular calcium. NR1/2A responses were inhibited by the noncompetitive antagonists MK-801 and dextromethorphan and were dependent on extracellular calcium but not on intracellular calcium stores. In contrast, no detectable intracellular calcium responses were observed in NR1/2C-transfected cells. These findings indicate that NMDA receptors in the absence of other neuron-specific factors can mediate increases in intracellular calcium with subunit specificity and extracellular calcium dependence.

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“…This illustrates that the increase in cAMP levels observed in the presence of NMDA was an NMDA receptor-mediated event. The potency of 7-chlorokynurenate is comparable with that cited in other investigations using this antagonist to block NMDA receptor activation (Perrier and Benavides, 1995).…”

Section: Discussionsupporting

confidence: 68%

A Common Signaling Pathway for Striatal NMDA and Adenosine A_2aReceptors: Implications for the Treatment of Parkinson's Disease

Nash

Brotchie

2000

J. Neurosci.

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The striatum is the major input region of the basal ganglia, playing a pivotal role in the selection, initiation, and coordination of movement both physiologically and in pathophysiological situations such as Parkinson's disease. In the present study, we characterize interactions between NMDA receptors, adenosine receptors, and cAMP signaling within the striatum. Both NMDA (100 M) and the adenosine A 2a receptor agonist CPCA (3 M) increased cAMP levels (218.9 Ϯ 19.9% and 395.7 Ϯ 67.2%, respectively; cf. basal). The NMDA-induced increase in cAMP was completely blocked when slices were preincubated with either the NMDA receptor antagonist 7-chlorokynurenate or the adenosine A 2 receptor antagonist DMPX (100 M), suggesting that striatal NMDA receptors increase cAMP indirectly via stimulation of adenosine A 2a receptors. Thus, NMDA receptors and adenosine A 2a receptors might share a common signaling pathway within the striatum. In striatal slices prepared from the 6-hydroxydopamine-lesioned rat model of Parkinson's disease, NMDA receptor-mediated increases in cAMP were greater on the lesioned side compared with the unlesioned side (349.6 Ϯ 40.2% compared with 200.9 Ϯ 21.9% of basal levels, respectively). This finding substantiates previous evidence implicating overactivity of striatal NMDA receptors in parkinsonism and suggests that a common NMDA receptor-adenosine A 2a receptor-cAMP signaling cascade might be an important mechanism responsible for mediating parkinsonian symptoms.

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Pharmacological heterogeneity of NMDA receptors in cerebellar granule cells in immature rat slices. A microfluorimetric study with the [Ca2+]i sensitive dye indo-1

Cited by 14 publications

References 27 publications

Active release of glycine or d‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse

Active release of glycine or d‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse

N-Methyl-D-aspartate Receptors Expressed in a Nonneuronal Cell Line Mediate Subunit-specific Increases in Free Intracellular Calcium

A Common Signaling Pathway for Striatal NMDA and Adenosine A_2aReceptors: Implications for the Treatment of Parkinson's Disease

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Pharmacological heterogeneity of NMDA receptors in cerebellar granule cells in immature rat slices. A microfluorimetric study with the [Ca2+]i sensitive dye indo-1

Cited by 14 publications

References 27 publications

Active release of glycine or d‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse

Active release of glycine or d‐serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse

N-Methyl-D-aspartate Receptors Expressed in a Nonneuronal Cell Line Mediate Subunit-specific Increases in Free Intracellular Calcium

A Common Signaling Pathway for Striatal NMDA and Adenosine A2aReceptors: Implications for the Treatment of Parkinson's Disease

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Product

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A Common Signaling Pathway for Striatal NMDA and Adenosine A_2aReceptors: Implications for the Treatment of Parkinson's Disease