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

Istituto di Ricerche Farmacologiche "Mario Negri"

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

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
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
Publication status	Published - May 22 1989

Keywords

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

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/0304-3940(89)90702-7

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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, n-Acetyl-aspartyl-glutamate (NAAG), Peptidase, Quisqualate, Striatum",

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

year = "1989",

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

language = "English",

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AU - Stauch, Barbara L.

AU - Robinson, Michael B.

AU - Forloni, Gianluigi

AU - Tsai, Guochuan

AU - Coyle, Joseph T.

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 - n-Acetyl-aspartyl-glutamate (NAAG)

KW - Peptidase

KW - Quisqualate

KW - Striatum

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

Abstract

Keywords

ASJC Scopus subject areas

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