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Synaptosomal transport of radiolabel from N-acetyl-aspartyl-(/sup 3/H)glutamate suggests a mechanism of inactivation of an excitatory neuropeptide

Journal Article:

Abstract

This study was undertaken to explore in synaptosomal preparations the disposition of N-acetyl-aspartyl-glutamate (NAAG), an endogenous acidic dipeptide neurotransmitter candidate. Radiolabel from N-acetyl-aspartyl(/sup 3/H)glutamate was taken up rapidly into an osmotically sensitive compartment by rat brain synaptosomal preparations in a sodium-, temperature-, and time-dependent manner. HPLC analysis of the accumulated radiolabel indicated that the bulk of the tritium cochromatographed with glutamic acid and not with NAAG. In contrast, (/sup 14/C)NAAG, labeled on the N-terminal acetate, was not taken up by the synaptosomal preparation. All effective inhibitors of synaptosomal, Na+-dependent (/sup 3/H)glutamate uptake were found to exhibit similar potency in inhibiting uptake of tritium derived from (/sup 3/H)NAAG. However, certain alpha-linked acidic dipeptides, structurally similar to NAAG, as well as the potent convulsant quisqualic acid inhibited synaptosomal transport of (/sup 3/H)NAAG but were ineffective as inhibitors of (/sup 3/H)glutamate transport. Together with a demonstration of disparities between the regional accumulation of radiolabel from (/sup 3/H)NAAG and high-affinity (/sup 3/H)glutamate uptake, these data suggest the presence in brain of a specific peptidase targeting carboxy-terminal glutamate-containing dipeptides that may be coupled to the Na+-dependent glutamate transporter. These findings provide a possible mechanism for NAAG inactivation subsequent to its release from nerve endings.
Publication Date:
Oct 01, 1986
Product Type:
Journal Article
Reference Number:
EDB-86-194647
Resource Relation:
Journal Name: J. Neurochem.; (United Kingdom); Journal Volume: 4
Subject:
59 BASIC BIOLOGICAL SCIENCES; CENTRAL NERVOUS SYSTEM AGENTS; MEMBRANE TRANSPORT; AMINO ACIDS; BRAIN; CARBON 14 COMPOUNDS; NERVE CELLS; OXADIAZOLES; RATS; SODIUM; TRITIUM COMPOUNDS; ALKALI METALS; ANIMAL CELLS; ANIMALS; AZOLES; BODY; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM; DRUGS; ELEMENTS; HETEROCYCLIC COMPOUNDS; LABELLED COMPOUNDS; MAMMALS; METALS; NERVOUS SYSTEM; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; ORGANS; RODENTS; SOMATIC CELLS; VERTEBRATES; 551001* - Physiological Systems- Tracer Techniques
OSTI ID:
5006643
Research Organizations:
Johns Hopkins Univ. School of Medicine, Baltimore, MD
Country of Origin:
United Kingdom
Language:
English
Other Identifying Numbers:
Journal ID: CODEN: JONRA
Submitting Site:
NLM
Size:
Pages: 1013-1019
Announcement Date:

Journal Article:

Citation Formats

Blakely, R D, Ory-Lavollee, L, Thompson, R C, and Coyle, J T. Synaptosomal transport of radiolabel from N-acetyl-aspartyl-(/sup 3/H)glutamate suggests a mechanism of inactivation of an excitatory neuropeptide. United Kingdom: N. p., 1986. Web.
Blakely, R D, Ory-Lavollee, L, Thompson, R C, & Coyle, J T. Synaptosomal transport of radiolabel from N-acetyl-aspartyl-(/sup 3/H)glutamate suggests a mechanism of inactivation of an excitatory neuropeptide. United Kingdom.
Blakely, R D, Ory-Lavollee, L, Thompson, R C, and Coyle, J T. 1986. "Synaptosomal transport of radiolabel from N-acetyl-aspartyl-(/sup 3/H)glutamate suggests a mechanism of inactivation of an excitatory neuropeptide." United Kingdom.
@misc{etde_5006643,
title = {Synaptosomal transport of radiolabel from N-acetyl-aspartyl-(/sup 3/H)glutamate suggests a mechanism of inactivation of an excitatory neuropeptide}
author = {Blakely, R D, Ory-Lavollee, L, Thompson, R C, and Coyle, J T}
abstractNote = {This study was undertaken to explore in synaptosomal preparations the disposition of N-acetyl-aspartyl-glutamate (NAAG), an endogenous acidic dipeptide neurotransmitter candidate. Radiolabel from N-acetyl-aspartyl(/sup 3/H)glutamate was taken up rapidly into an osmotically sensitive compartment by rat brain synaptosomal preparations in a sodium-, temperature-, and time-dependent manner. HPLC analysis of the accumulated radiolabel indicated that the bulk of the tritium cochromatographed with glutamic acid and not with NAAG. In contrast, (/sup 14/C)NAAG, labeled on the N-terminal acetate, was not taken up by the synaptosomal preparation. All effective inhibitors of synaptosomal, Na+-dependent (/sup 3/H)glutamate uptake were found to exhibit similar potency in inhibiting uptake of tritium derived from (/sup 3/H)NAAG. However, certain alpha-linked acidic dipeptides, structurally similar to NAAG, as well as the potent convulsant quisqualic acid inhibited synaptosomal transport of (/sup 3/H)NAAG but were ineffective as inhibitors of (/sup 3/H)glutamate transport. Together with a demonstration of disparities between the regional accumulation of radiolabel from (/sup 3/H)NAAG and high-affinity (/sup 3/H)glutamate uptake, these data suggest the presence in brain of a specific peptidase targeting carboxy-terminal glutamate-containing dipeptides that may be coupled to the Na+-dependent glutamate transporter. These findings provide a possible mechanism for NAAG inactivation subsequent to its release from nerve endings.}
journal = {J. Neurochem.; (United Kingdom)}
volume = {4}
journal type = {AC}
place = {United Kingdom}
year = {1986}
month = {Oct}
}