The effects of N-acetylated alpha-linked acidic dipeptidase (NAALADase) inhibitors on [3H]NAAG catabolism in vivo.
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 t1/2 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.
Stauch
B L
BL
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore 21205.
Robinson
M B
MB
Forloni
G
G
Tsai
G
G
Coyle
J T
JT
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004150:Dipeptidases / Q000378:metabolism / Q000502:physiology*; D004151:Dipeptides / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D043425:Glutamate Carboxypeptidase II; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D013997:Time Factors
D004151:Dipeptides; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; C027172:isospaglumic acid; D016318:Quisqualic Acid; D004150:Dipeptidases; D043425:Glutamate Carboxypeptidase II; D004229:Dithiothreitol