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Regulation of glutamate carboxypeptidase II hydrolysis of N ‐acetylaspartylglutamate (NAAG) in crayfish nervous tissue is mediated by glial glutamate and acetylcholine receptors
Author(s) -
Urazaev Albert K.,
Grossfeld Robert M.,
Lieberman Edward M.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03041.x
Subject(s) - glutamate carboxypeptidase ii , glutamate receptor , crayfish , acetylcholine , chemistry , metabotropic glutamate receptor , nervous tissue , neuroscience , carboxypeptidase , nervous system , receptor , biochemistry , medicine , endocrinology , biology , enzyme , prostate , cancer , fishery
Glutamate carboxypeptidase II (GCPII), a glial ectoenzyme, is responsible for N ‐acetylaspartylglutamate (NAAG) hydrolysis. Its regulation in crayfish nervous tissue was investigated by examining uptake of [ 3 H]glutamate derived from N ‐acetylaspartyl‐[ 3 H]glutamate ([ 3 H]NAAG) to measure GCPII activity. Electrical stimulation (100 Hz, 10 min) during 30 min incubation with [ 3 H]NAAG increased tissue [ 3 H]glutamate tenfold. This was prevented by 2‐(phosphonomethyl)‐pentanedioic acid (2‐PMPA), a GCPII inhibitor, suggesting that stimulation increased the hydrolysis of [ 3 H]NAAG and metabolic recycling of [ 3 H]glutamate. Antagonists of glial group II metabotropic glutamate receptors (mGLUR II ), NMDA receptors and acetylcholine (ACh) receptors that mediate axon–glia signaling in crayfish nerve fibers decreased the effect of stimulation by 58–83%, suggesting that glial receptor activation leads to stimulation of GCPII activity. In combination, they reduced [ 3 H]NAAG hydrolysis during stimulation to unstimulated control levels. Agonist stimulation of mGLUR II mimicked the effect of electrical stimulation, and was prevented by antagonists of GCPII or mGLUR II . Raising extracellular K + to three times the normal level stimulated [ 3 H]NAAG release and GCPII activity. These effects were also blocked by antagonists of GCPII and mGLUR II . No receptor antagonist or agonist tested or 2‐PMPA affected uptake of [ 3 H]glutamate. We conclude that NAAG released from stimulated nerve fibers activates its own hydrolysis via stimulation of GCPII activity mediated through glial mGLUR II, NMDA and ACh receptors.