Polyamines potentiate responses of N-methyl-D-aspartate receptors expressed in Xenopus oocytes

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Abstract

Glutamate, the major excitatory neurotransmitter in the central nervous system, activates at least three types of channel-forming receptors defined by the selective agonists N-methyl-D-aspartate (NMDA), kainate, and quisqualate [or more selectively by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)]. Activation of the NMDA receptor requires glycine as well as NMDA or glutamate. Recent studies have provided evidence that certain polyamines potentiate the binding by NMDA receptors of glycine and the open channel blocker MK-801. To determine whether polyamines alter channel opening, we examined their effects on rat brain glutamate receptors expressed in Xenopus oocytes. Our results demonstrate that spermine potentiates the response of the NMDA receptor but has no effect on responses to kainate and quisqualate. Furthermore, spermine increases the maximum response to NMDA and glycine and acts, at least in part, by increasing the apparent affinity of the NMDA receptor/channel complex for glycine. The present findings and the fact that polyamines are a natural constituent of brain suggest that polyamines may play a role in the regulation of glutamatergic transmission.

Original languageEnglish (US)
Pages (from-to)9971-9974
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number24
StatePublished - 1990

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Polyamines
Xenopus
N-Methyl-D-Aspartate Receptors
Oocytes
N-Methylaspartate
Glycine
Quisqualic Acid
Spermine
Kainic Acid
Sarcosine
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Dizocilpine Maleate
Glutamate Receptors
Brain
Neurotransmitter Agents
Glutamic Acid
Central Nervous System
Acids

Keywords

  • Excitatory neurotransmitter
  • Glutamate
  • Spermine
  • Synaptic transmission

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "Polyamines potentiate responses of N-methyl-D-aspartate receptors expressed in Xenopus oocytes",
abstract = "Glutamate, the major excitatory neurotransmitter in the central nervous system, activates at least three types of channel-forming receptors defined by the selective agonists N-methyl-D-aspartate (NMDA), kainate, and quisqualate [or more selectively by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)]. Activation of the NMDA receptor requires glycine as well as NMDA or glutamate. Recent studies have provided evidence that certain polyamines potentiate the binding by NMDA receptors of glycine and the open channel blocker MK-801. To determine whether polyamines alter channel opening, we examined their effects on rat brain glutamate receptors expressed in Xenopus oocytes. Our results demonstrate that spermine potentiates the response of the NMDA receptor but has no effect on responses to kainate and quisqualate. Furthermore, spermine increases the maximum response to NMDA and glycine and acts, at least in part, by increasing the apparent affinity of the NMDA receptor/channel complex for glycine. The present findings and the fact that polyamines are a natural constituent of brain suggest that polyamines may play a role in the regulation of glutamatergic transmission.",
keywords = "Excitatory neurotransmitter, Glutamate, Spermine, Synaptic transmission",
author = "McGurk, {James F.} and Bennett, {Michael V. L.} and Zukin, {R. Suzanne}",
year = "1990",
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T1 - Polyamines potentiate responses of N-methyl-D-aspartate receptors expressed in Xenopus oocytes

AU - McGurk, James F.

AU - Bennett, Michael V. L.

AU - Zukin, R. Suzanne

PY - 1990

Y1 - 1990

N2 - Glutamate, the major excitatory neurotransmitter in the central nervous system, activates at least three types of channel-forming receptors defined by the selective agonists N-methyl-D-aspartate (NMDA), kainate, and quisqualate [or more selectively by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)]. Activation of the NMDA receptor requires glycine as well as NMDA or glutamate. Recent studies have provided evidence that certain polyamines potentiate the binding by NMDA receptors of glycine and the open channel blocker MK-801. To determine whether polyamines alter channel opening, we examined their effects on rat brain glutamate receptors expressed in Xenopus oocytes. Our results demonstrate that spermine potentiates the response of the NMDA receptor but has no effect on responses to kainate and quisqualate. Furthermore, spermine increases the maximum response to NMDA and glycine and acts, at least in part, by increasing the apparent affinity of the NMDA receptor/channel complex for glycine. The present findings and the fact that polyamines are a natural constituent of brain suggest that polyamines may play a role in the regulation of glutamatergic transmission.

AB - Glutamate, the major excitatory neurotransmitter in the central nervous system, activates at least three types of channel-forming receptors defined by the selective agonists N-methyl-D-aspartate (NMDA), kainate, and quisqualate [or more selectively by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)]. Activation of the NMDA receptor requires glycine as well as NMDA or glutamate. Recent studies have provided evidence that certain polyamines potentiate the binding by NMDA receptors of glycine and the open channel blocker MK-801. To determine whether polyamines alter channel opening, we examined their effects on rat brain glutamate receptors expressed in Xenopus oocytes. Our results demonstrate that spermine potentiates the response of the NMDA receptor but has no effect on responses to kainate and quisqualate. Furthermore, spermine increases the maximum response to NMDA and glycine and acts, at least in part, by increasing the apparent affinity of the NMDA receptor/channel complex for glycine. The present findings and the fact that polyamines are a natural constituent of brain suggest that polyamines may play a role in the regulation of glutamatergic transmission.

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KW - Synaptic transmission

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