N-Methyl-D-aspartate activates different channels than do kainate and quisqualate

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

In the mammalian central nervous system, the excitatory amino acid transmitter L-glutamate activates three pharmacologically distinguishable receptors, the N-methyl-D-aspartate (NMDA), kainate, and quisqualate receptors. The present paper addresses the issue of whether these three receptors operate independent channels or whether they share channels that may have several conductance substates. The Xenopus oocyte provides a system for expression of exogenous mRNAs that permits detailed study of receptor structure and function. In oocytes injected with rat brain mRNA, NMDA has a stoichiometry of channel activation different from that for kainate and quisqualate. NMDA activates its own channels as indicated by simple summation or near-summation of currents evoked by NMDA with those evoked by quisqualate or kainate. Deviations from summation are ascribable to lack of selectivity in which an agonist at one receptor acts as a weak antagonist at another receptor. A further indication of separate channels is that block of NMDA channels by Mg2+ or phencyclidine has no effect on kainate or quisqualate responses evoked during the block. Interactions of kainate and quisqualate are more complex, but they can be explained by lack of complete specificity of these agonists for their own receptors.

Original languageEnglish (US)
Pages (from-to)2083-2087
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number6
StatePublished - 1989

Fingerprint

Quisqualic Acid
Kainic Acid
N-Methylaspartate
Oocytes
Kainic Acid Receptors
Phencyclidine
Messenger RNA
Excitatory Amino Acids
AMPA Receptors
Xenopus
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Central Nervous System
Brain

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

@article{87e9913083da496bb04dde2e0b568694,
title = "N-Methyl-D-aspartate activates different channels than do kainate and quisqualate",
abstract = "In the mammalian central nervous system, the excitatory amino acid transmitter L-glutamate activates three pharmacologically distinguishable receptors, the N-methyl-D-aspartate (NMDA), kainate, and quisqualate receptors. The present paper addresses the issue of whether these three receptors operate independent channels or whether they share channels that may have several conductance substates. The Xenopus oocyte provides a system for expression of exogenous mRNAs that permits detailed study of receptor structure and function. In oocytes injected with rat brain mRNA, NMDA has a stoichiometry of channel activation different from that for kainate and quisqualate. NMDA activates its own channels as indicated by simple summation or near-summation of currents evoked by NMDA with those evoked by quisqualate or kainate. Deviations from summation are ascribable to lack of selectivity in which an agonist at one receptor acts as a weak antagonist at another receptor. A further indication of separate channels is that block of NMDA channels by Mg2+ or phencyclidine has no effect on kainate or quisqualate responses evoked during the block. Interactions of kainate and quisqualate are more complex, but they can be explained by lack of complete specificity of these agonists for their own receptors.",
author = "J. Lerma and L. Kushner and Zukin, {R. Suzanne} and Bennett, {Michael V. L.}",
year = "1989",
language = "English (US)",
volume = "86",
pages = "2083--2087",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "6",

}

TY - JOUR

T1 - N-Methyl-D-aspartate activates different channels than do kainate and quisqualate

AU - Lerma, J.

AU - Kushner, L.

AU - Zukin, R. Suzanne

AU - Bennett, Michael V. L.

PY - 1989

Y1 - 1989

N2 - In the mammalian central nervous system, the excitatory amino acid transmitter L-glutamate activates three pharmacologically distinguishable receptors, the N-methyl-D-aspartate (NMDA), kainate, and quisqualate receptors. The present paper addresses the issue of whether these three receptors operate independent channels or whether they share channels that may have several conductance substates. The Xenopus oocyte provides a system for expression of exogenous mRNAs that permits detailed study of receptor structure and function. In oocytes injected with rat brain mRNA, NMDA has a stoichiometry of channel activation different from that for kainate and quisqualate. NMDA activates its own channels as indicated by simple summation or near-summation of currents evoked by NMDA with those evoked by quisqualate or kainate. Deviations from summation are ascribable to lack of selectivity in which an agonist at one receptor acts as a weak antagonist at another receptor. A further indication of separate channels is that block of NMDA channels by Mg2+ or phencyclidine has no effect on kainate or quisqualate responses evoked during the block. Interactions of kainate and quisqualate are more complex, but they can be explained by lack of complete specificity of these agonists for their own receptors.

AB - In the mammalian central nervous system, the excitatory amino acid transmitter L-glutamate activates three pharmacologically distinguishable receptors, the N-methyl-D-aspartate (NMDA), kainate, and quisqualate receptors. The present paper addresses the issue of whether these three receptors operate independent channels or whether they share channels that may have several conductance substates. The Xenopus oocyte provides a system for expression of exogenous mRNAs that permits detailed study of receptor structure and function. In oocytes injected with rat brain mRNA, NMDA has a stoichiometry of channel activation different from that for kainate and quisqualate. NMDA activates its own channels as indicated by simple summation or near-summation of currents evoked by NMDA with those evoked by quisqualate or kainate. Deviations from summation are ascribable to lack of selectivity in which an agonist at one receptor acts as a weak antagonist at another receptor. A further indication of separate channels is that block of NMDA channels by Mg2+ or phencyclidine has no effect on kainate or quisqualate responses evoked during the block. Interactions of kainate and quisqualate are more complex, but they can be explained by lack of complete specificity of these agonists for their own receptors.

UR - http://www.scopus.com/inward/record.url?scp=0024516458&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024516458&partnerID=8YFLogxK

M3 - Article

VL - 86

SP - 2083

EP - 2087

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 6

ER -