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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.
Mol Pharmacol. 1990 Apr; 37(4):572-7.MP

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 microM. The order of potency in enhancing [3H]TCP binding was N,N'-bis(3-aminopropyl)-1,3-propanediamine greater than N,N'-bis-(3-aminopropyl)-ethylenediamine greater than spermine greater than spermidine greater than 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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2157963

Citation

Sacaan, A I., and K M. Johnson. "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." Molecular Pharmacology, vol. 37, no. 4, 1990, pp. 572-7.
Sacaan AI, Johnson KM. 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. Mol Pharmacol. 1990;37(4):572-7.
Sacaan, A. I., & Johnson, K. M. (1990). 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. Molecular Pharmacology, 37(4), 572-7.
Sacaan AI, Johnson KM. 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. Mol Pharmacol. 1990;37(4):572-7. PubMed PMID: 2157963.
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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,A I, AU - Johnson,K M, PY - 1990/4/1/pubmed PY - 1990/4/1/medline PY - 1990/4/1/entrez SP - 572 EP - 7 JF - Molecular pharmacology JO - Mol Pharmacol VL - 37 IS - 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 microM. The order of potency in enhancing [3H]TCP binding was N,N'-bis(3-aminopropyl)-1,3-propanediamine greater than N,N'-bis-(3-aminopropyl)-ethylenediamine greater than spermine greater than spermidine greater than 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. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/2157963/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_ DB - PRIME DP - Unbound Medicine ER -