The effects of N-acetylated alpha-linked acidic dipeptidase (NAALADase) inhibitors on [3H]NAAG catabolism in vivo

Barbara L. Stauch; Michael B. Robinson; Gianluigi Forloni; Guochuan Tsai; Joseph T. Coyle

doi:10.1016/0304-3940(89)90702-7

The effects of N-acetylated alpha-linked acidic dipeptidase (NAALADase) inhibitors on [³H]NAAG catabolism in vivo

Barbara L. Stauch, Michael B. Robinson, Gianluigi Forloni, Guochuan Tsai, Joseph T. Coyle

School of Medicine

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

N-Acetylated, alpha-linked acidic dipeptidase (NAALADase) is a chloride-activated, membrane bound, metallopeptidase that cleaves the endogenous neuropeptide N-acetyl-aspartyl-glutamate (NAAG) in vitro. To determine whether NAALADase is the catabolic enzyme of NAAG in vivo, we have examined the effects on [³H]NAAG metabolism of intrastriatal co-injections of agents that affect NAALADase activity in vitro. Co-injections of NAALADase inhibitors, such as quisqualate (Quis), phosphate, dithiothreitol and EGTA were found to prolong the t_{1 2} of [³H]NAAG, whereas cobalt, a NAALADase activity stimulator, accelerated [³H]NAAG catabolism. These results are consistent with a role for NAALADase in the extracellular disposition of endogenous NAAG.

Original language	English (US)
Pages (from-to)	295-300
Number of pages	6
Journal	Neuroscience Letters
Volume	100
Issue number	1-3
DOIs	https://doi.org/10.1016/0304-3940(89)90702-7
State	Published - May 22 1989

Keywords

Excitatory neurotransmission
Glutamate
Peptidase
Quisqualate
Striatum
n-Acetyl-aspartyl-glutamate (NAAG)

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/0304-3940(89)90702-7

Cite this

@article{189e2144e0414a1683f0d1a72fb79178,

title = "The effects of N-acetylated alpha-linked acidic dipeptidase (NAALADase) inhibitors on [3H]NAAG catabolism in vivo",

abstract = "N-Acetylated, alpha-linked acidic dipeptidase (NAALADase) is a chloride-activated, membrane bound, metallopeptidase that cleaves the endogenous neuropeptide N-acetyl-aspartyl-glutamate (NAAG) in vitro. To determine whether NAALADase is the catabolic enzyme of NAAG in vivo, we have examined the effects on [3H]NAAG metabolism of intrastriatal co-injections of agents that affect NAALADase activity in vitro. Co-injections of NAALADase inhibitors, such as quisqualate (Quis), phosphate, dithiothreitol and EGTA were found to prolong the t 1 2 of [3H]NAAG, whereas cobalt, a NAALADase activity stimulator, accelerated [3H]NAAG catabolism. These results are consistent with a role for NAALADase in the extracellular disposition of endogenous NAAG.",

keywords = "Excitatory neurotransmission, Glutamate, Peptidase, Quisqualate, Striatum, n-Acetyl-aspartyl-glutamate (NAAG)",

author = "Stauch, {Barbara L.} and Robinson, {Michael B.} and Gianluigi Forloni and Guochuan Tsai and Coyle, {Joseph T.}",

note = "Funding Information: We thank Alice Trawinski for her excellent secretarial assistance. This research was supported by USHPS Grant NS ! 3584 and the NIH/NIGMS Pharmacology Training Grant 2 T32 GM07626-1 I. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",

year = "1989",

month = may,

day = "22",

doi = "10.1016/0304-3940(89)90702-7",

language = "English (US)",

volume = "100",

pages = "295--300",

journal = "Neuroscience Letters",

issn = "0304-3940",

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T1 - The effects of N-acetylated alpha-linked acidic dipeptidase (NAALADase) inhibitors on [3H]NAAG catabolism in vivo

AU - Stauch, Barbara L.

AU - Robinson, Michael B.

AU - Forloni, Gianluigi

AU - Tsai, Guochuan

AU - Coyle, Joseph T.

N1 - Funding Information: We thank Alice Trawinski for her excellent secretarial assistance. This research was supported by USHPS Grant NS ! 3584 and the NIH/NIGMS Pharmacology Training Grant 2 T32 GM07626-1 I. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 1989/5/22

Y1 - 1989/5/22

N2 - N-Acetylated, alpha-linked acidic dipeptidase (NAALADase) is a chloride-activated, membrane bound, metallopeptidase that cleaves the endogenous neuropeptide N-acetyl-aspartyl-glutamate (NAAG) in vitro. To determine whether NAALADase is the catabolic enzyme of NAAG in vivo, we have examined the effects on [3H]NAAG metabolism of intrastriatal co-injections of agents that affect NAALADase activity in vitro. Co-injections of NAALADase inhibitors, such as quisqualate (Quis), phosphate, dithiothreitol and EGTA were found to prolong the t 1 2 of [3H]NAAG, whereas cobalt, a NAALADase activity stimulator, accelerated [3H]NAAG catabolism. These results are consistent with a role for NAALADase in the extracellular disposition of endogenous NAAG.

AB - N-Acetylated, alpha-linked acidic dipeptidase (NAALADase) is a chloride-activated, membrane bound, metallopeptidase that cleaves the endogenous neuropeptide N-acetyl-aspartyl-glutamate (NAAG) in vitro. To determine whether NAALADase is the catabolic enzyme of NAAG in vivo, we have examined the effects on [3H]NAAG metabolism of intrastriatal co-injections of agents that affect NAALADase activity in vitro. Co-injections of NAALADase inhibitors, such as quisqualate (Quis), phosphate, dithiothreitol and EGTA were found to prolong the t 1 2 of [3H]NAAG, whereas cobalt, a NAALADase activity stimulator, accelerated [3H]NAAG catabolism. These results are consistent with a role for NAALADase in the extracellular disposition of endogenous NAAG.

KW - Excitatory neurotransmission

KW - Glutamate

KW - Peptidase

KW - Quisqualate

KW - Striatum

KW - n-Acetyl-aspartyl-glutamate (NAAG)

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