Characterization of the stimulatory and inhibitory effects of polyamines on [3H]N-(1-[thienyl]cyclohexyl) piperidine binding to the N-Methyl-D-aspartate receptor ionophore complex

Aida I. Sacaan, Kenneth M. Johnson

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Spermidine and spermine, as well as several other structurally related compounds, were tested in a [3H]N-(1-[thienyl]cyclohexyl) piperidine ([3H]TCP) binding assay to determine the structural requirements of polyamines for activation of the N-methyl-D-aspartate-operated ion channel. Under nonequilibrium conditions, the polyamines enhanced [3H]TCP binding approximately 9-fold, with EC50 values ranging from 0.8 to 60 μM. The order of potency in enhancing [3H]TCP binding was N,N′-bis(3-aminopropyl)-1,3-propanediamine > N,N′-bis-(3-aminopropyl)-ethylenediamine > spermine > spermidine > N,N′-bis-(2-aminoethyl)-1,3-propanediamine. 1,3-Diaminopropane produced a partial agonistic effect, whereas putrescine, cadaverine, and 1,7-diaminoheptane were without effect at concentrations up to 1 mM. Eadie-Hofstee analysis of spermidine-induced [3H]TCP binding at equilibrium revealed a 3-fold increase in the affinity without a significant change in receptor density. This was further supported by kinetic data that showed that spermidine produced an increase in the association rate and a decrease in the dissociation rate of [3H]TCP binding to its site. Putrescine, cadaverine, and 1,3-diaminopropane antagonized the effects of spermidine by an apparently noncompetitive mechanism. Magnesium ions mimicked the effects of putrescine, suggesting the possibility that the inhibitory effects of Mg2+ and putrescine are mechanistically related.

Original languageEnglish (US)
Pages (from-to)572-577
Number of pages6
JournalMolecular Pharmacology
Volume37
Issue number4
StatePublished - Apr 1990

Fingerprint

Spermidine
Ionophores
Polyamines
N-Methyl-D-Aspartate Receptors
Putrescine
Cadaverine
ethylenediamine
Spermine
N-Methylaspartate
Ion Channels
Magnesium
piperidine
Ions

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{c667560ff9304654b71cc4a8439d2cc8,
title = "Characterization of the stimulatory and inhibitory effects of polyamines on [3H]N-(1-[thienyl]cyclohexyl) piperidine binding to the N-Methyl-D-aspartate receptor ionophore complex",
abstract = "Spermidine and spermine, as well as several other structurally related compounds, were tested in a [3H]N-(1-[thienyl]cyclohexyl) piperidine ([3H]TCP) binding assay to determine the structural requirements of polyamines for activation of the N-methyl-D-aspartate-operated ion channel. Under nonequilibrium conditions, the polyamines enhanced [3H]TCP binding approximately 9-fold, with EC50 values ranging from 0.8 to 60 μM. The order of potency in enhancing [3H]TCP binding was N,N′-bis(3-aminopropyl)-1,3-propanediamine > N,N′-bis-(3-aminopropyl)-ethylenediamine > spermine > spermidine > N,N′-bis-(2-aminoethyl)-1,3-propanediamine. 1,3-Diaminopropane produced a partial agonistic effect, whereas putrescine, cadaverine, and 1,7-diaminoheptane were without effect at concentrations up to 1 mM. Eadie-Hofstee analysis of spermidine-induced [3H]TCP binding at equilibrium revealed a 3-fold increase in the affinity without a significant change in receptor density. This was further supported by kinetic data that showed that spermidine produced an increase in the association rate and a decrease in the dissociation rate of [3H]TCP binding to its site. Putrescine, cadaverine, and 1,3-diaminopropane antagonized the effects of spermidine by an apparently noncompetitive mechanism. Magnesium ions mimicked the effects of putrescine, suggesting the possibility that the inhibitory effects of Mg2+ and putrescine are mechanistically related.",
author = "Sacaan, {Aida I.} and Johnson, {Kenneth M.}",
year = "1990",
month = "4",
language = "English (US)",
volume = "37",
pages = "572--577",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "4",

}

TY - JOUR

T1 - Characterization of the stimulatory and inhibitory effects of polyamines on [3H]N-(1-[thienyl]cyclohexyl) piperidine binding to the N-Methyl-D-aspartate receptor ionophore complex

AU - Sacaan, Aida I.

AU - Johnson, Kenneth M.

PY - 1990/4

Y1 - 1990/4

N2 - Spermidine and spermine, as well as several other structurally related compounds, were tested in a [3H]N-(1-[thienyl]cyclohexyl) piperidine ([3H]TCP) binding assay to determine the structural requirements of polyamines for activation of the N-methyl-D-aspartate-operated ion channel. Under nonequilibrium conditions, the polyamines enhanced [3H]TCP binding approximately 9-fold, with EC50 values ranging from 0.8 to 60 μM. The order of potency in enhancing [3H]TCP binding was N,N′-bis(3-aminopropyl)-1,3-propanediamine > N,N′-bis-(3-aminopropyl)-ethylenediamine > spermine > spermidine > N,N′-bis-(2-aminoethyl)-1,3-propanediamine. 1,3-Diaminopropane produced a partial agonistic effect, whereas putrescine, cadaverine, and 1,7-diaminoheptane were without effect at concentrations up to 1 mM. Eadie-Hofstee analysis of spermidine-induced [3H]TCP binding at equilibrium revealed a 3-fold increase in the affinity without a significant change in receptor density. This was further supported by kinetic data that showed that spermidine produced an increase in the association rate and a decrease in the dissociation rate of [3H]TCP binding to its site. Putrescine, cadaverine, and 1,3-diaminopropane antagonized the effects of spermidine by an apparently noncompetitive mechanism. Magnesium ions mimicked the effects of putrescine, suggesting the possibility that the inhibitory effects of Mg2+ and putrescine are mechanistically related.

AB - Spermidine and spermine, as well as several other structurally related compounds, were tested in a [3H]N-(1-[thienyl]cyclohexyl) piperidine ([3H]TCP) binding assay to determine the structural requirements of polyamines for activation of the N-methyl-D-aspartate-operated ion channel. Under nonequilibrium conditions, the polyamines enhanced [3H]TCP binding approximately 9-fold, with EC50 values ranging from 0.8 to 60 μM. The order of potency in enhancing [3H]TCP binding was N,N′-bis(3-aminopropyl)-1,3-propanediamine > N,N′-bis-(3-aminopropyl)-ethylenediamine > spermine > spermidine > N,N′-bis-(2-aminoethyl)-1,3-propanediamine. 1,3-Diaminopropane produced a partial agonistic effect, whereas putrescine, cadaverine, and 1,7-diaminoheptane were without effect at concentrations up to 1 mM. Eadie-Hofstee analysis of spermidine-induced [3H]TCP binding at equilibrium revealed a 3-fold increase in the affinity without a significant change in receptor density. This was further supported by kinetic data that showed that spermidine produced an increase in the association rate and a decrease in the dissociation rate of [3H]TCP binding to its site. Putrescine, cadaverine, and 1,3-diaminopropane antagonized the effects of spermidine by an apparently noncompetitive mechanism. Magnesium ions mimicked the effects of putrescine, suggesting the possibility that the inhibitory effects of Mg2+ and putrescine are mechanistically related.

UR - http://www.scopus.com/inward/record.url?scp=0025273692&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025273692&partnerID=8YFLogxK

M3 - Article

C2 - 2157963

AN - SCOPUS:0025273692

VL - 37

SP - 572

EP - 577

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 4

ER -