Competitive inhibition of magnesium-induced [3H]N-(1-[Thienyl] cyclohexyl)piperidine binding by arcaine: Evidence for a shared spermidine-magnesium binding site

Aida I. Sacaan, Kenneth M. Johnson

Research output: Contribution to journalArticle

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Abstract

The polyamine competitive antagonist arcaine (1,4-diguanidinobutane) produced complete inhibition of basal [3H]N-(1-[thienyl] cyclohexyl)piperidine ([3H]TCP) binding, with an IC50 value of 4.52 ± 0.93 μM. Arcaine (5 and 10 μM) produced a decrease in the affinity without a significant change in the receptor density of [3H]TCP binding under equilibrium conditions. In addition, arcaine did not alter either N-methyl-D-aspartate-specific [3H] glutamate or strychnine-insensitive [3H]glycine binding. Furthermore, increasing concentrations of arcaine produced parallel rightward shifts in the concentration-response curves for both spermidine- and magnesium-induced [3H]TCP binding, suggesting that arcaine is a competitive inhibitor of both agonists. Similar rightward shifts were observed for barium- and strontium-induced [3H]TCP binding. In contrast, arcaine decreased the efficacy of glutamate- and glycine-induced [3H]TCP binding without changing their EC50 values, indicating a noncompetitive type of inhibition. These results imply that spermidine and certain divalent cations including magnesium share the same mechanism for enhancing [3H]TCP binding, whereas glutamate and glycine have different sites of action. This is further supported by the additive effect of spermidine when tested in the presence of maximal concentrations of glutamate and glycine. On the other hand, spermidine and magnesium were not additive and, in fact, magnesium was able to block the effects of spermidine under certain conditions. The possibility that magnesium is a partial agonist at the polyamine site is discussed.

Original languageEnglish (US)
Pages (from-to)705-710
Number of pages6
JournalMolecular Pharmacology
Volume38
Issue number5
StatePublished - Nov 1990

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Spermidine
Magnesium
Binding Sites
Glycine
Glutamic Acid
Polyamines
Strychnine
Strontium
Divalent Cations
N-Methylaspartate
Barium
arcaine
piperidine
Inhibitory Concentration 50

ASJC Scopus subject areas

  • Pharmacology

Cite this

Competitive inhibition of magnesium-induced [3H]N-(1-[Thienyl] cyclohexyl)piperidine binding by arcaine : Evidence for a shared spermidine-magnesium binding site. / Sacaan, Aida I.; Johnson, Kenneth M.

In: Molecular Pharmacology, Vol. 38, No. 5, 11.1990, p. 705-710.

Research output: Contribution to journalArticle

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abstract = "The polyamine competitive antagonist arcaine (1,4-diguanidinobutane) produced complete inhibition of basal [3H]N-(1-[thienyl] cyclohexyl)piperidine ([3H]TCP) binding, with an IC50 value of 4.52 ± 0.93 μM. Arcaine (5 and 10 μM) produced a decrease in the affinity without a significant change in the receptor density of [3H]TCP binding under equilibrium conditions. In addition, arcaine did not alter either N-methyl-D-aspartate-specific [3H] glutamate or strychnine-insensitive [3H]glycine binding. Furthermore, increasing concentrations of arcaine produced parallel rightward shifts in the concentration-response curves for both spermidine- and magnesium-induced [3H]TCP binding, suggesting that arcaine is a competitive inhibitor of both agonists. Similar rightward shifts were observed for barium- and strontium-induced [3H]TCP binding. In contrast, arcaine decreased the efficacy of glutamate- and glycine-induced [3H]TCP binding without changing their EC50 values, indicating a noncompetitive type of inhibition. These results imply that spermidine and certain divalent cations including magnesium share the same mechanism for enhancing [3H]TCP binding, whereas glutamate and glycine have different sites of action. This is further supported by the additive effect of spermidine when tested in the presence of maximal concentrations of glutamate and glycine. On the other hand, spermidine and magnesium were not additive and, in fact, magnesium was able to block the effects of spermidine under certain conditions. The possibility that magnesium is a partial agonist at the polyamine site is discussed.",
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