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Title: Spermidine reverses arcaine's inhibition of N-methyl-D-aspartate-induced hippocampal ( sup 3 H)norepinephrine release

The inhibition of N-methyl-D-aspartate (NMDA)-induced ({sup 3}H)norepinephrine (({sup 3}H)NE) release by a putrescine analog was studied. We report that arcaine, diguanidinobutane, a putative competitive polyamine antagonist, completely and noncompetitively antagonized NMDA-induced ({sup 3}H)NE release from rat hippocampal minces with an IC50 value of 102 microM. Arcaine did not alter kainate- or potassium-induced ({sup 3}H)NE release suggesting a specific effect on NMDA-mediated responses. Spermidine did not alter NMDA-induced ({sup 3}H)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.
Authors:
;  [1]
  1. (Univ. of Texas Medical Branch, Galveston (USA))
Publication Date:
OSTI Identifier:
6152306
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA); Journal Volume: 255:3
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ASPARTIC ACID; RECEPTORS; NORADRENALINE; SECRETION; PUTRESCINE; BIOCHEMICAL REACTION KINETICS; SPERMIDINE; CELL MEMBRANES; HIPPOCAMPUS; INHIBITION; RATS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ADRENAL HORMONES; AMINES; AMINO ACIDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; BRAIN; CARBOXYLIC ACIDS; CARDIOTONICS; CARDIOVASCULAR AGENTS; CELL CONSTITUENTS; CENTRAL NERVOUS SYSTEM; DRUGS; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; KINETICS; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; REACTION KINETICS; RODENTS; SYMPATHOMIMETICS; VERTEBRATES 550201* -- Biochemistry-- Tracer Techniques