Equilibrium analysis of [3H]TCP binding

effects of glycine, magnesium and N-methyl-D-aspartate agonists

Kenneth M. Johnson, Aida I. Sacaan, Lawrence D. Snell

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

It has been reported that glutamate can increase the binding of [3H]TCP to phencyclidine (PCP) receptors by an action on receptors which are selective for N-methyl-D-aspartate (NMDA). Recently this laboratory has reported that glycine and magnesium can amplify this effect of NMDA agonists in well-washed, lysed cortical membranes. Here we report that maximally effective concentrations of glutamate (10 μM), NMDA (300 μM), MgCl2 (300 μM) and glycine (10 μM) increase the affinity of the PCP receptor for [3H]TCP by approximately 4-fold in the absence of any change in the density of PCP receptors. However, in combination with glutamate, magnesium had the further effect of increasing the Bmax by about 75%. Finally, a synaptosomal P2 preparation, which had not been washed to minimize the concentration of endogenous effectors had a Bmax value similar to the well-washed preparation, but had a KD value 8-fold lower. These data indicate that the primary effect of NMDA agonists, glycine, and low concentrations of magnesium ions is to convert the PCP receptor from a low-affinity to a high-affinity state. These data are discussed in relation to the functional regulation of the NMDA ionophore.

Original languageEnglish (US)
Pages (from-to)141-146
Number of pages6
JournalEuropean Journal of Pharmacology
Volume152
Issue number1-2
DOIs
StatePublished - Jul 26 1988

Fingerprint

Phencyclidine Receptors
N-Methylaspartate
Glycine
Magnesium
Glutamic Acid
Magnesium Chloride
Ionophores
Ions
Membranes

Keywords

  • (Rat)
  • Cortex
  • Glutamate
  • Glycine
  • Magnesium
  • N-Methyl-D-aspartate
  • Phencyclidine (PCP) receptors

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Equilibrium analysis of [3H]TCP binding : effects of glycine, magnesium and N-methyl-D-aspartate agonists. / Johnson, Kenneth M.; Sacaan, Aida I.; Snell, Lawrence D.

In: European Journal of Pharmacology, Vol. 152, No. 1-2, 26.07.1988, p. 141-146.

Research output: Contribution to journalArticle

Johnson, Kenneth M. ; Sacaan, Aida I. ; Snell, Lawrence D. / Equilibrium analysis of [3H]TCP binding : effects of glycine, magnesium and N-methyl-D-aspartate agonists. In: European Journal of Pharmacology. 1988 ; Vol. 152, No. 1-2. pp. 141-146.
@article{ca3e5feec0b24b948126989cb1b91824,
title = "Equilibrium analysis of [3H]TCP binding: effects of glycine, magnesium and N-methyl-D-aspartate agonists",
abstract = "It has been reported that glutamate can increase the binding of [3H]TCP to phencyclidine (PCP) receptors by an action on receptors which are selective for N-methyl-D-aspartate (NMDA). Recently this laboratory has reported that glycine and magnesium can amplify this effect of NMDA agonists in well-washed, lysed cortical membranes. Here we report that maximally effective concentrations of glutamate (10 μM), NMDA (300 μM), MgCl2 (300 μM) and glycine (10 μM) increase the affinity of the PCP receptor for [3H]TCP by approximately 4-fold in the absence of any change in the density of PCP receptors. However, in combination with glutamate, magnesium had the further effect of increasing the Bmax by about 75{\%}. Finally, a synaptosomal P2 preparation, which had not been washed to minimize the concentration of endogenous effectors had a Bmax value similar to the well-washed preparation, but had a KD value 8-fold lower. These data indicate that the primary effect of NMDA agonists, glycine, and low concentrations of magnesium ions is to convert the PCP receptor from a low-affinity to a high-affinity state. These data are discussed in relation to the functional regulation of the NMDA ionophore.",
keywords = "(Rat), Cortex, Glutamate, Glycine, Magnesium, N-Methyl-D-aspartate, Phencyclidine (PCP) receptors",
author = "Johnson, {Kenneth M.} and Sacaan, {Aida I.} and Snell, {Lawrence D.}",
year = "1988",
month = "7",
day = "26",
doi = "10.1016/0014-2999(88)90845-X",
language = "English (US)",
volume = "152",
pages = "141--146",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Equilibrium analysis of [3H]TCP binding

T2 - effects of glycine, magnesium and N-methyl-D-aspartate agonists

AU - Johnson, Kenneth M.

AU - Sacaan, Aida I.

AU - Snell, Lawrence D.

PY - 1988/7/26

Y1 - 1988/7/26

N2 - It has been reported that glutamate can increase the binding of [3H]TCP to phencyclidine (PCP) receptors by an action on receptors which are selective for N-methyl-D-aspartate (NMDA). Recently this laboratory has reported that glycine and magnesium can amplify this effect of NMDA agonists in well-washed, lysed cortical membranes. Here we report that maximally effective concentrations of glutamate (10 μM), NMDA (300 μM), MgCl2 (300 μM) and glycine (10 μM) increase the affinity of the PCP receptor for [3H]TCP by approximately 4-fold in the absence of any change in the density of PCP receptors. However, in combination with glutamate, magnesium had the further effect of increasing the Bmax by about 75%. Finally, a synaptosomal P2 preparation, which had not been washed to minimize the concentration of endogenous effectors had a Bmax value similar to the well-washed preparation, but had a KD value 8-fold lower. These data indicate that the primary effect of NMDA agonists, glycine, and low concentrations of magnesium ions is to convert the PCP receptor from a low-affinity to a high-affinity state. These data are discussed in relation to the functional regulation of the NMDA ionophore.

AB - It has been reported that glutamate can increase the binding of [3H]TCP to phencyclidine (PCP) receptors by an action on receptors which are selective for N-methyl-D-aspartate (NMDA). Recently this laboratory has reported that glycine and magnesium can amplify this effect of NMDA agonists in well-washed, lysed cortical membranes. Here we report that maximally effective concentrations of glutamate (10 μM), NMDA (300 μM), MgCl2 (300 μM) and glycine (10 μM) increase the affinity of the PCP receptor for [3H]TCP by approximately 4-fold in the absence of any change in the density of PCP receptors. However, in combination with glutamate, magnesium had the further effect of increasing the Bmax by about 75%. Finally, a synaptosomal P2 preparation, which had not been washed to minimize the concentration of endogenous effectors had a Bmax value similar to the well-washed preparation, but had a KD value 8-fold lower. These data indicate that the primary effect of NMDA agonists, glycine, and low concentrations of magnesium ions is to convert the PCP receptor from a low-affinity to a high-affinity state. These data are discussed in relation to the functional regulation of the NMDA ionophore.

KW - (Rat)

KW - Cortex

KW - Glutamate

KW - Glycine

KW - Magnesium

KW - N-Methyl-D-aspartate

KW - Phencyclidine (PCP) receptors

UR - http://www.scopus.com/inward/record.url?scp=0023822157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023822157&partnerID=8YFLogxK

U2 - 10.1016/0014-2999(88)90845-X

DO - 10.1016/0014-2999(88)90845-X

M3 - Article

VL - 152

SP - 141

EP - 146

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-2

ER -