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

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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 t12 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.

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Present address: Departments of Pediatrics and Pharmacology, Children's Seashore House, University of Pennsylvania, Philadelphia, PA 19014, U.S.A.

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Present address: Instituto di Ricerche Farmacologiche, ‘Mario Negri’, Via Eritrea 62, 20157 Milan, Italy.

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