Polyamines regulate glycine interaction with the N‐methyl‐ D ‐aspartate receptor

Polyamines regulate glycine interaction with the N‐methyl‐ D ‐aspartate receptor (3H)Glycine blinding studies have been performed to further characterize polyamine interactions with the rat brain N‐methyl‐D‐asparate (NMDA) receptor. Strychnine‐insensitive (3H)glycine binding to washed cortical membranes was enhanced by spermine, spermidine, and hirudonin. Spermine stimulation of binding was additive with that produced by the NMDA receptor agonist L‐glutamate. A high concentration of the L‐glutamate antagonist 2‐amino‐5‐phosphonovaleric acid reduced, but did not eliminate, spermine effects. Saturation experiments indicated that L‐glutamate and spermine enhancement of binding was due to an increase in (3H)glycine binding affinity. Kinetic studies showed that optimal concentrations of spermine and L‐glutamate reduced (3H)glycine association and dissociation rates by approximately fivefold and 30‐fold, respectively. In competition experiments, the presence of L‐glutamate and spermine had differential effects on the affinites of compounds that act as either agonists or antagonists at the glycine site of the NMDA receptor. The affinities of the agonists glycine, D‐serine, and Dalanine, were increased about fivefold, while antagonist (HA‐966, 7‐chlorokynurenic acid) inhibitory potencies were unchanged. These data support our previous results showing that the NMDA receptor possesses a novel polyamine recognition site and demonstrate that these compounds directly modulate glycine's interactions with the receptor complex. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Synapse Wiley

Polyamines regulate glycine interaction with the N‐methyl‐ D ‐aspartate receptor

Synapse, Volume 5 (4) – Jan 1, 1990

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Publisher
Wiley
Copyright
Copyright © 1990 Wiley‐Liss, Inc.
ISSN
0887-4476
eISSN
1098-2396
D.O.I.
10.1002/syn.890050406
Publisher site
See Article on Publisher Site

Abstract

(3H)Glycine blinding studies have been performed to further characterize polyamine interactions with the rat brain N‐methyl‐D‐asparate (NMDA) receptor. Strychnine‐insensitive (3H)glycine binding to washed cortical membranes was enhanced by spermine, spermidine, and hirudonin. Spermine stimulation of binding was additive with that produced by the NMDA receptor agonist L‐glutamate. A high concentration of the L‐glutamate antagonist 2‐amino‐5‐phosphonovaleric acid reduced, but did not eliminate, spermine effects. Saturation experiments indicated that L‐glutamate and spermine enhancement of binding was due to an increase in (3H)glycine binding affinity. Kinetic studies showed that optimal concentrations of spermine and L‐glutamate reduced (3H)glycine association and dissociation rates by approximately fivefold and 30‐fold, respectively. In competition experiments, the presence of L‐glutamate and spermine had differential effects on the affinites of compounds that act as either agonists or antagonists at the glycine site of the NMDA receptor. The affinities of the agonists glycine, D‐serine, and Dalanine, were increased about fivefold, while antagonist (HA‐966, 7‐chlorokynurenic acid) inhibitory potencies were unchanged. These data support our previous results showing that the NMDA receptor possesses a novel polyamine recognition site and demonstrate that these compounds directly modulate glycine's interactions with the receptor complex.

Journal

SynapseWiley

Published: Jan 1, 1990

References

  • The novel anticonvulsant MK‐801 binds to the activated state of the N‐methyl‐ D ‐aspartate receptor in rat brain
    Foster, Foster; Wong, Wong
  • The regional distribution of the polyamines spermidine and spermine in brain
    Shaw, Shaw; Pateman, Pateman

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