Regulation of glutamate carboxypeptidase II hydrolysis of N‐acetylaspartylglutamate (NAAG) in crayfish nervous tissue is mediated by glial glutamate and …

AK Urazaev, RM Grossfeld… - Journal of …, 2005 - Wiley Online Library
AK Urazaev, RM Grossfeld, EM Lieberman
Journal of neurochemistry, 2005Wiley Online Library
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 [3H] glutamate derived from N‐acetylaspartyl‐[3H]
glutamate ([3H] NAAG) to measure GCPII activity. Electrical stimulation (100 Hz, 10 min)
during 30 min incubation with [3H] NAAG increased tissue [3H] glutamate tenfold. This was
prevented by 2‐(phosphonomethyl)‐pentanedioic acid (2‐PMPA), a GCPII inhibitor …
Abstract
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 [3H]glutamate derived from N‐acetylaspartyl‐[3H]glutamate ([3H]NAAG) to measure GCPII activity. Electrical stimulation (100 Hz, 10 min) during 30 min incubation with [3H]NAAG increased tissue [3H]glutamate tenfold. This was prevented by 2‐(phosphonomethyl)‐pentanedioic acid (2‐PMPA), a GCPII inhibitor, suggesting that stimulation increased the hydrolysis of [3H]NAAG and metabolic recycling of [3H]glutamate. Antagonists of glial group II metabotropic glutamate receptors (mGLURII), 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 [3H]NAAG hydrolysis during stimulation to unstimulated control levels. Agonist stimulation of mGLURII mimicked the effect of electrical stimulation, and was prevented by antagonists of GCPII or mGLURII. Raising extracellular K+ to three times the normal level stimulated [3H]NAAG release and GCPII activity. These effects were also blocked by antagonists of GCPII and mGLURII. No receptor antagonist or agonist tested or 2‐PMPA affected uptake of [3H]glutamate. We conclude that NAAG released from stimulated nerve fibers activates its own hydrolysis via stimulation of GCPII activity mediated through glial mGLURII, NMDA and ACh receptors.
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