Spermidine reverses arcaine's inhibition of N-methyl-D-aspartate-induced hippocampal [3H]norepinephrine release

A. I. Sacaan, K. M. Johnson

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The inhibition of N-methyl-D-aspartate (NMDA)-induced [3H]norepinephrine ([3HNE) release by a putrescine analog was studied. We report that arcaine, diguanidinobutane, a putative competitive polyamine antagonist, completely and noncompetitively antagonized NMDA-induced [3H]NE release from rat hippocampal minces with an IC50 value of 102 μM. Arcaine did not alter kainate- or potassium-induced [3H]NE release suggesting a specific effect on NMDA-mediated responses. Spermidine did not alter NMDA-induced [3H]NE release, nor did it reverse the effect of arcaine when introduced in a normal physiologic superfusion buffer. However, spermidine reversed the effect of arcaine when superfusing with buffer that contained 5% (v/v) of the organic solvent dimethylsulfoxide. This finding suggests that the polyamine site may be located at the intracellular surface of the cell membrane. Our results provide the first evidence for polyamine modulation of the NMDA receptor ionophore complex in a functional physiologic system.

Original languageEnglish (US)
Pages (from-to)1060-1063
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume255
Issue number3
StatePublished - 1990

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Spermidine
N-Methylaspartate
Norepinephrine
Polyamines
Buffers
Putrescine
Kainic Acid
Ionophores
Dimethyl Sulfoxide
N-Methyl-D-Aspartate Receptors
Inhibitory Concentration 50
Potassium
Cell Membrane
arcaine

ASJC Scopus subject areas

  • Pharmacology

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Spermidine reverses arcaine's inhibition of N-methyl-D-aspartate-induced hippocampal [3H]norepinephrine release. / Sacaan, A. I.; Johnson, K. M.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 255, No. 3, 1990, p. 1060-1063.

Research output: Contribution to journalArticle

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abstract = "The inhibition of N-methyl-D-aspartate (NMDA)-induced [3H]norepinephrine ([3HNE) release by a putrescine analog was studied. We report that arcaine, diguanidinobutane, a putative competitive polyamine antagonist, completely and noncompetitively antagonized NMDA-induced [3H]NE release from rat hippocampal minces with an IC50 value of 102 μM. Arcaine did not alter kainate- or potassium-induced [3H]NE release suggesting a specific effect on NMDA-mediated responses. Spermidine did not alter NMDA-induced [3H]NE release, nor did it reverse the effect of arcaine when introduced in a normal physiologic superfusion buffer. However, spermidine reversed the effect of arcaine when superfusing with buffer that contained 5{\%} (v/v) of the organic solvent dimethylsulfoxide. This finding suggests that the polyamine site may be located at the intracellular surface of the cell membrane. Our results provide the first evidence for polyamine modulation of the NMDA receptor ionophore complex in a functional physiologic system.",
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