Competitive antagonism at metabotropic glutamate receptors by (S) -4-carboxyphenylglycine and (RS) -α-methyl-4-carboxyphenylglycine

Eaton, S.A.; Jane, David E.; Jones, Philip L.; Porter, Richard H.; Pook, Peter C.K.; Sunter, David; Udvarhelyi, Peter M.; Roberts, Peter; Salt, Thomas E.; Watkins, Johnathan

doi:10.1016/0922-4106(93)90028-8

Cited by 224 publications

(92 citation statements)

References 4 publications

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“…1S,3R-ACPD effects were blocked by MCPG, a competitive mGluR antagonist (Eaton et al, 1993;Jane et al, 1993). After MCPG addition to the spinal cord bath (Ͼ7 min), the effect of local application of 1S,3R-ACPD was attenuated, albeit at high concentrations of MCPG.…”

Section: S3r-acpd-induced Bimodal Changes In Respiratory Motor Outputmentioning

confidence: 92%

Multiple Actions of 1S,3R-ACPD in Modulating Endogenous Synaptic Transmission to Spinal Respiratory Motoneurons

Dong¹,

Morin²,

Feldman

1996

J. Neurosci.

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To determine physiological roles of metabotropic glutamate receptors (mGluRs) affecting breathing, we examined the effects of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) on synaptic transmission and excitability of phrenic motoneurons (PMNs) in an in vitro neonatal rat brainstem/spinal cord preparation. The effects of 1S,3R-ACPD were multiple, including reduction of inspiratory-modulated synaptic currents and increase of neuronal excitability via an inward current (I acpd ) associated with a decrease of membrane conductance. The mechanism underlying synaptic depression was examined. We found that 1S,3R-ACPD reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents. The current induced by exogenous AMPA was not significantly affected by 1S,3R-ACPD. These results suggest that 1S,3R-ACPD-induced reduction of inspiratory synaptic currents is mediated by presynaptic mGluRs. We also examined the ionic basis for I acpd . We found that I acpd had a reversal potential of approximately Ϫ100 mV, close to the estimated E K ϩ (Ϫ95 mV). Elevating extracellular [K ϩ ] to 9 mM reduced the I acpd reversal potential to Ϫ75 mV. The K ϩ channel blocker Ba 2ϩ induced an inward current with a reversal potential at Ϫ93 mV associated with a decrease of membrane conductance, closely resembling the effect of 1S,3R-ACPD. Moreover, Ba 2ϩ occluded 1S,3R-ACPD effects. In the presence of Ba 2ϩ , I acpd and the 1S,3R-ACPD-induced decrease of membrane conductance were diminished. Our data indicate that the dominant component of I acpd results from the blockade of a Ba 2ϩ -sensitive resting K ϩ conductance. We conclude that the activation of mGluRs affects the inspiratory-modulated activity of PMNs via distinct mechanisms at pre-and postsynaptic sites.

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Section: S3r-acpd-induced Bimodal Changes In Respiratory Motor Outputmentioning

confidence: 92%

Multiple Actions of 1S,3R-ACPD in Modulating Endogenous Synaptic Transmission to Spinal Respiratory Motoneurons

Dong¹,

Morin²,

Feldman

1996

J. Neurosci.

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“…Because glutamate is the major neurotransmitter released at Schaffer collateral synapses (Collingridge et al, 1983), we first examined whether glutamatergic antagonists were able to block the astrocytic responses to Schaffer collateral stimulation. In the presence of both 3 mM kynurenic acid (KY), which blocks ionotropic glutamate receptors, and 1 mM MCPG, which selectively blocks metabotropic glutamate receptors (Eaton et al, 1993), the astrocytic responses were reversibly inhibited in 67% (51/76 astrocytes, 2 slices; Fig. 5A).…”

Section: The Astrocytic Responses Are Attributable To Neuronal Glutammentioning

confidence: 99%

Hippocampal AstrocytesIn SituRespond to Glutamate Released from Synaptic Terminals

1996

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A long-standing question in neurobiology is whether astrocytes respond to the neuronal release of neurotransmitters in vivo. To address this question, acutely isolated hippocampal slices were loaded with the calcium-sensitive dye Calcium Green-1 and the responses of the astrocytes to electrical stimulation of the Schaffer collaterals were monitored by confocal microscopy. To confirm that the responsive cells were astrocytes, the slices were immunostained for the astrocytic marker glial fibrillary acidic protein. Stimulation of the Schaffer collaterals (50 Hz, 2 sec) resulted in increases in the concentration of intracellular calcium ([Ca 2ϩ ] i ) in the astrocytes located in the stratum radiatum of CA1. The astrocytic responses were blocked by the sodium channel blocker tetrodotoxin, the voltage-dependent calcium channel blocker -conotoxin-MVIIC, and the selective metabotropic glutamate receptor antagonist ␣-methyl-4-carboxyphenylglycine (MCPG). These results suggest that the astrocytic responses were induced by stimulation of metabotropic glutamate receptors on the astrocytes by neuronally released glutamate. The astrocytic responses to neuronal stimulation were enhanced in the presence of the K ϩ channel antagonist 4-aminopyridine (4-AP). Inhibition of the astrocytic responses in the presence of 4-AP required the presence of both MCPG and the ionotropic glutamate receptor antagonist kynurenic acid. These results suggest that higher levels of neuronal activity result in stimulation of both metabotropic and ionotropic glutamate receptors on the astrocytes. Overall, the results indicate that hippocampal astrocytes in situ are able to respond to the neuronal release of the neurotransmitter glutamate with increases in [Ca 2ϩ ] i .

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“…In those papers the active compounds were named cyclopropylglutamate stereoisomers (CGA), to stress the analogy with glutamate; (lS,3S,4S)-CGA corresponded to L-CGA B and is here named L-CCG-I. The nomenclature used by Shinozaki et al (1989) (Ito et al, 1992;Eaton et al, 1993;Birse et al, 1993).…”

Section: Methodsmentioning

confidence: 99%

Pharmacological characterization of the metabotropic glutamate receptor inhibiting d‐[³H]‐aspartate output in rat striatum

Lombardi

Alesiani

Leonardi

et al. 1993

British J Pharmacology

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Competitive antagonism at metabotropic glutamate receptors by (S) -4-carboxyphenylglycine and (RS) -α-methyl-4-carboxyphenylglycine

Cited by 224 publications

References 4 publications

Multiple Actions of 1S,3R-ACPD in Modulating Endogenous Synaptic Transmission to Spinal Respiratory Motoneurons

Multiple Actions of 1S,3R-ACPD in Modulating Endogenous Synaptic Transmission to Spinal Respiratory Motoneurons

Hippocampal AstrocytesIn SituRespond to Glutamate Released from Synaptic Terminals

Pharmacological characterization of the metabotropic glutamate receptor inhibiting d‐[³H]‐aspartate output in rat striatum

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Competitive antagonism at metabotropic glutamate receptors by (S) -4-carboxyphenylglycine and (RS) -α-methyl-4-carboxyphenylglycine

Cited by 224 publications

References 4 publications

Multiple Actions of 1S,3R-ACPD in Modulating Endogenous Synaptic Transmission to Spinal Respiratory Motoneurons

Multiple Actions of 1S,3R-ACPD in Modulating Endogenous Synaptic Transmission to Spinal Respiratory Motoneurons

Hippocampal AstrocytesIn SituRespond to Glutamate Released from Synaptic Terminals

Pharmacological characterization of the metabotropic glutamate receptor inhibiting d‐[3H]‐aspartate output in rat striatum

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Pharmacological characterization of the metabotropic glutamate receptor inhibiting d‐[³H]‐aspartate output in rat striatum