Spermidine attenuation of volatile anesthetic inhibition of glutamate-stimulated [3H](5D, 10S)-(+)-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine ([3H]MK-801) binding to N-methyl-D-aspartate (NMDA) receptors in rat brain

Dan C Martin, Robert S. Aronstam

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The influence of spermidine, a polyamine agonist, on volatile anesthetic inhibition of N-methyl-D-aspartate (NMDA) receptor activation, as indicated by glutamate stimulation of [3H]MK-801 ([3H](5D,10S)-(+)-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine) binding, was studied in rat brain. Spermidine reserved the inhibition caused by four volatile anesthetics (enflurane, halothane, methoxyflurane and chloroform) at the same concentrations (EC50 ≈ 3 μM) at which it potentiated glutamate opening of the NMDA ion channel. The anesthetics had no effect on the direct stimulation of channel opening by spermidine, which occurred at concentrations of spermidine greater than 30 μM in the absence of receptor agonist. In these actions, spermidine closely resembled the allosteric co-agonist glycine. The present results suggest that anesthetic action on NMDA receptors involves a set of sites on the channel complex that is distinct from the recognition sites for glutamate, glycine, and channel blockers, and are consistent with the idea that blockade of NMDA receptors contributes to the development of the anesthetic state.

Original languageEnglish (US)
Pages (from-to)1373-1377
Number of pages5
JournalBiochemical Pharmacology
Volume50
Issue number9
DOIs
StatePublished - Oct 26 1995

Fingerprint

Imines
Spermidine
Dizocilpine Maleate
N-Methyl-D-Aspartate Receptors
Anesthetics
Rats
Glutamic Acid
Brain
Glycine
Methoxyflurane
Enflurane
Polyamines
Halothane
N-Methylaspartate
Chloroform
Ion Channels
Chemical activation

Keywords

  • anesthesia
  • anesthetics
  • dizocilpine
  • ion channel
  • MK-801
  • NMDA receptors
  • polyamines
  • spermidine

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

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title = "Spermidine attenuation of volatile anesthetic inhibition of glutamate-stimulated [3H](5D, 10S)-(+)-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine ([3H]MK-801) binding to N-methyl-D-aspartate (NMDA) receptors in rat brain",
abstract = "The influence of spermidine, a polyamine agonist, on volatile anesthetic inhibition of N-methyl-D-aspartate (NMDA) receptor activation, as indicated by glutamate stimulation of [3H]MK-801 ([3H](5D,10S)-(+)-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine) binding, was studied in rat brain. Spermidine reserved the inhibition caused by four volatile anesthetics (enflurane, halothane, methoxyflurane and chloroform) at the same concentrations (EC50 ≈ 3 μM) at which it potentiated glutamate opening of the NMDA ion channel. The anesthetics had no effect on the direct stimulation of channel opening by spermidine, which occurred at concentrations of spermidine greater than 30 μM in the absence of receptor agonist. In these actions, spermidine closely resembled the allosteric co-agonist glycine. The present results suggest that anesthetic action on NMDA receptors involves a set of sites on the channel complex that is distinct from the recognition sites for glutamate, glycine, and channel blockers, and are consistent with the idea that blockade of NMDA receptors contributes to the development of the anesthetic state.",
keywords = "anesthesia, anesthetics, dizocilpine, ion channel, MK-801, NMDA receptors, polyamines, spermidine",
author = "Martin, {Dan C} and Aronstam, {Robert S.}",
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T1 - Spermidine attenuation of volatile anesthetic inhibition of glutamate-stimulated [3H](5D, 10S)-(+)-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine ([3H]MK-801) binding to N-methyl-D-aspartate (NMDA) receptors in rat brain

AU - Martin, Dan C

AU - Aronstam, Robert S.

PY - 1995/10/26

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N2 - The influence of spermidine, a polyamine agonist, on volatile anesthetic inhibition of N-methyl-D-aspartate (NMDA) receptor activation, as indicated by glutamate stimulation of [3H]MK-801 ([3H](5D,10S)-(+)-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine) binding, was studied in rat brain. Spermidine reserved the inhibition caused by four volatile anesthetics (enflurane, halothane, methoxyflurane and chloroform) at the same concentrations (EC50 ≈ 3 μM) at which it potentiated glutamate opening of the NMDA ion channel. The anesthetics had no effect on the direct stimulation of channel opening by spermidine, which occurred at concentrations of spermidine greater than 30 μM in the absence of receptor agonist. In these actions, spermidine closely resembled the allosteric co-agonist glycine. The present results suggest that anesthetic action on NMDA receptors involves a set of sites on the channel complex that is distinct from the recognition sites for glutamate, glycine, and channel blockers, and are consistent with the idea that blockade of NMDA receptors contributes to the development of the anesthetic state.

AB - The influence of spermidine, a polyamine agonist, on volatile anesthetic inhibition of N-methyl-D-aspartate (NMDA) receptor activation, as indicated by glutamate stimulation of [3H]MK-801 ([3H](5D,10S)-(+)-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine) binding, was studied in rat brain. Spermidine reserved the inhibition caused by four volatile anesthetics (enflurane, halothane, methoxyflurane and chloroform) at the same concentrations (EC50 ≈ 3 μM) at which it potentiated glutamate opening of the NMDA ion channel. The anesthetics had no effect on the direct stimulation of channel opening by spermidine, which occurred at concentrations of spermidine greater than 30 μM in the absence of receptor agonist. In these actions, spermidine closely resembled the allosteric co-agonist glycine. The present results suggest that anesthetic action on NMDA receptors involves a set of sites on the channel complex that is distinct from the recognition sites for glutamate, glycine, and channel blockers, and are consistent with the idea that blockade of NMDA receptors contributes to the development of the anesthetic state.

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