Volatile anesthetics and NMDA receptors. Enflurane inhibition of glutamate-stimulated [3H]MK-801 binding and reversal by glycine

Dan C. Martin, Jacob E. Abraham, Marc Plagenhoef, Robert S. Aronstam

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The influence of enflurane, a volatile general anesthetic, on [3H]MK-801 binding to a site in the ion channel of the N-methyl-d-aspartate (NMDA) receptor was determined in membranes from rat cerebral cortex. Enflurane disrupted glutamate stimulation of [3H]MK-801 (1 nM) binding with an IC50 of 0.4 mM. This inhibition was associated with a decrease in receptor affinity with no change in the number of [3H]MK-801 binding sites. Basal [3H]MK-801 binding measured in the absence of glutamate was not affected by enflurane. In contrast, [3H]CGS-19775 binding to the glutamate recognition site on the NMDA receptor was only weakly inhibited by enflurane (e.g., less than 20% inhibition of 5 nM [3H]CGS binding by 1.2 mM enflurane). Glycine, a positive allosteric NMDA receptor modulator, markedly attenuated the inhibition of glutamate-stimulated [3H]MK-801 binding by enflurane, with an EC50 of approximately 0.8 μM. Thus, enflurane selectively inhibits glutamate activation of the NMDA receptors, and an allosteric modulator attenuates this action. These effects could reflect anesthetic action at the glycine binding site or at another, undefined site which influences activation of the ion channel. These findings raise the possibility that inhibition of transmission at NMDA receptors contributes to the development of the anesthetic state.

Original languageEnglish (US)
Pages (from-to)73-76
Number of pages4
JournalNeuroscience Letters
Volume132
Issue number1
DOIs
StatePublished - Oct 28 1991

Fingerprint

Enflurane
Dizocilpine Maleate
Glycine
Anesthetics
Glutamic Acid
Ion Channels
Binding Sites
General Anesthetics
aspartic acid receptor
Cerebral Cortex
Inhibitory Concentration 50
Membranes

Keywords

  • Anesthetic
  • Enflurane
  • Glutamate
  • Glycine
  • MK-801
  • N-Methyl-d-aspartate receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Volatile anesthetics and NMDA receptors. Enflurane inhibition of glutamate-stimulated [3H]MK-801 binding and reversal by glycine. / Martin, Dan C.; Abraham, Jacob E.; Plagenhoef, Marc; Aronstam, Robert S.

In: Neuroscience Letters, Vol. 132, No. 1, 28.10.1991, p. 73-76.

Research output: Contribution to journalArticle

@article{7439d80c6c264193b4ba00f291d48434,
title = "Volatile anesthetics and NMDA receptors. Enflurane inhibition of glutamate-stimulated [3H]MK-801 binding and reversal by glycine",
abstract = "The influence of enflurane, a volatile general anesthetic, on [3H]MK-801 binding to a site in the ion channel of the N-methyl-d-aspartate (NMDA) receptor was determined in membranes from rat cerebral cortex. Enflurane disrupted glutamate stimulation of [3H]MK-801 (1 nM) binding with an IC50 of 0.4 mM. This inhibition was associated with a decrease in receptor affinity with no change in the number of [3H]MK-801 binding sites. Basal [3H]MK-801 binding measured in the absence of glutamate was not affected by enflurane. In contrast, [3H]CGS-19775 binding to the glutamate recognition site on the NMDA receptor was only weakly inhibited by enflurane (e.g., less than 20{\%} inhibition of 5 nM [3H]CGS binding by 1.2 mM enflurane). Glycine, a positive allosteric NMDA receptor modulator, markedly attenuated the inhibition of glutamate-stimulated [3H]MK-801 binding by enflurane, with an EC50 of approximately 0.8 μM. Thus, enflurane selectively inhibits glutamate activation of the NMDA receptors, and an allosteric modulator attenuates this action. These effects could reflect anesthetic action at the glycine binding site or at another, undefined site which influences activation of the ion channel. These findings raise the possibility that inhibition of transmission at NMDA receptors contributes to the development of the anesthetic state.",
keywords = "Anesthetic, Enflurane, Glutamate, Glycine, MK-801, N-Methyl-d-aspartate receptor",
author = "Martin, {Dan C.} and Abraham, {Jacob E.} and Marc Plagenhoef and Aronstam, {Robert S.}",
year = "1991",
month = "10",
day = "28",
doi = "10.1016/0304-3940(91)90436-W",
language = "English (US)",
volume = "132",
pages = "73--76",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Volatile anesthetics and NMDA receptors. Enflurane inhibition of glutamate-stimulated [3H]MK-801 binding and reversal by glycine

AU - Martin, Dan C.

AU - Abraham, Jacob E.

AU - Plagenhoef, Marc

AU - Aronstam, Robert S.

PY - 1991/10/28

Y1 - 1991/10/28

N2 - The influence of enflurane, a volatile general anesthetic, on [3H]MK-801 binding to a site in the ion channel of the N-methyl-d-aspartate (NMDA) receptor was determined in membranes from rat cerebral cortex. Enflurane disrupted glutamate stimulation of [3H]MK-801 (1 nM) binding with an IC50 of 0.4 mM. This inhibition was associated with a decrease in receptor affinity with no change in the number of [3H]MK-801 binding sites. Basal [3H]MK-801 binding measured in the absence of glutamate was not affected by enflurane. In contrast, [3H]CGS-19775 binding to the glutamate recognition site on the NMDA receptor was only weakly inhibited by enflurane (e.g., less than 20% inhibition of 5 nM [3H]CGS binding by 1.2 mM enflurane). Glycine, a positive allosteric NMDA receptor modulator, markedly attenuated the inhibition of glutamate-stimulated [3H]MK-801 binding by enflurane, with an EC50 of approximately 0.8 μM. Thus, enflurane selectively inhibits glutamate activation of the NMDA receptors, and an allosteric modulator attenuates this action. These effects could reflect anesthetic action at the glycine binding site or at another, undefined site which influences activation of the ion channel. These findings raise the possibility that inhibition of transmission at NMDA receptors contributes to the development of the anesthetic state.

AB - The influence of enflurane, a volatile general anesthetic, on [3H]MK-801 binding to a site in the ion channel of the N-methyl-d-aspartate (NMDA) receptor was determined in membranes from rat cerebral cortex. Enflurane disrupted glutamate stimulation of [3H]MK-801 (1 nM) binding with an IC50 of 0.4 mM. This inhibition was associated with a decrease in receptor affinity with no change in the number of [3H]MK-801 binding sites. Basal [3H]MK-801 binding measured in the absence of glutamate was not affected by enflurane. In contrast, [3H]CGS-19775 binding to the glutamate recognition site on the NMDA receptor was only weakly inhibited by enflurane (e.g., less than 20% inhibition of 5 nM [3H]CGS binding by 1.2 mM enflurane). Glycine, a positive allosteric NMDA receptor modulator, markedly attenuated the inhibition of glutamate-stimulated [3H]MK-801 binding by enflurane, with an EC50 of approximately 0.8 μM. Thus, enflurane selectively inhibits glutamate activation of the NMDA receptors, and an allosteric modulator attenuates this action. These effects could reflect anesthetic action at the glycine binding site or at another, undefined site which influences activation of the ion channel. These findings raise the possibility that inhibition of transmission at NMDA receptors contributes to the development of the anesthetic state.

KW - Anesthetic

KW - Enflurane

KW - Glutamate

KW - Glycine

KW - MK-801

KW - N-Methyl-d-aspartate receptor

UR - http://www.scopus.com/inward/record.url?scp=0026062655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026062655&partnerID=8YFLogxK

U2 - 10.1016/0304-3940(91)90436-W

DO - 10.1016/0304-3940(91)90436-W

M3 - Article

C2 - 1686307

AN - SCOPUS:0026062655

VL - 132

SP - 73

EP - 76

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 1

ER -