Mechanisms for clearance of released N-acetylaspartylglutamate in crayfish nerve fibers: Implications for axon-glia signaling

A. Kh Urazaev, J. G. Buttram, J. P. Deen, B. Sh Gafurov, Barbara Slusher, R. M. Grossfeld, E. M. Lieberman

Research output: Contribution to journalArticle

Abstract

Crayfish nerve fibers incubated with radiolabeled glutamate or glutamine accumulate these substrates and synthesize radioactive N-acetylaspartylglutamate (NAAG). Upon stimulation of the medial giant nerve fiber, NAAG is the primary radioactive metabolite released. Since NAAG activates a glial hyperpolarization comparable to that initiated by glutamate or axonal stimulation through the same receptor, we have proposed that it is the likely mediator of interactions between the medial giant axon and its periaxonal glia. This manuscript reports investigations of possible mechanisms for termination of NAAG-signaling activity. N-acetylaspartyl-[3H]glutamate was not accumulated from the bath saline by unstimulated crayfish giant axons or their associated glia during a 30-min incubation. Stimulation of the central nerve cord at 50 Hz during the last minute of the incubation dramatically increased the levels of radiolabeled glutamate, NAAG, and glutamine in the medial giant axon and its associated glia. These results indicate that stimulation-sensitive peptide hydrolysis and metabolic recycling of the radiolabeled glutamate occurred. There was a β-NAAG-, quisqualate- and 2-(phosphonomethyl)-pentanedioic acid-inhibitable glutamate carboxypeptidase II activity in the membrane fraction of central nerve fibers, but not in axonal or glial cytoplasmic fractions. Inactivation of this enzyme by 2-(phosphonomethyl)-pentanedioic acid or inhibition of N-methyl-D-aspartate (NMDA) receptors by MK801 reduced the glial hyperpolarization activated by high-frequency stimulation. These results indicate that axon-to-glia signaling is terminated by NAAG hydrolysis and that the glutamate formed contributes to the glial electrical response in part via activation of NMDA receptors. Both NAAG release and an increase in glutamate carboxypeptidase II activity appear to be induced by nerve stimulation.

Original languageEnglish (US)
Pages (from-to)697-703
Number of pages7
JournalNeuroscience
Volume107
Issue number4
DOIs
StatePublished - Nov 28 2001
Externally publishedYes

Fingerprint

Astacoidea
Nerve Fibers
Neuroglia
Axons
Glutamic Acid
Glutamate Carboxypeptidase II
N-Methyl-D-Aspartate Receptors
Glutamine
Hydrolysis
Quisqualic Acid
N-acetyl-1-aspartylglutamic acid
Recycling
Baths
Peptides
Membranes
Enzymes

Keywords

  • Axon
  • Glia
  • Glutamate
  • Glutamate carboxypeptidase II
  • N-acetylaspartylglutamate
  • Transport

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mechanisms for clearance of released N-acetylaspartylglutamate in crayfish nerve fibers : Implications for axon-glia signaling. / Urazaev, A. Kh; Buttram, J. G.; Deen, J. P.; Gafurov, B. Sh; Slusher, Barbara; Grossfeld, R. M.; Lieberman, E. M.

In: Neuroscience, Vol. 107, No. 4, 28.11.2001, p. 697-703.

Research output: Contribution to journalArticle

Urazaev, A. Kh ; Buttram, J. G. ; Deen, J. P. ; Gafurov, B. Sh ; Slusher, Barbara ; Grossfeld, R. M. ; Lieberman, E. M. / Mechanisms for clearance of released N-acetylaspartylglutamate in crayfish nerve fibers : Implications for axon-glia signaling. In: Neuroscience. 2001 ; Vol. 107, No. 4. pp. 697-703.
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AU - Urazaev, A. Kh

AU - Buttram, J. G.

AU - Deen, J. P.

AU - Gafurov, B. Sh

AU - Slusher, Barbara

AU - Grossfeld, R. M.

AU - Lieberman, E. M.

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N2 - Crayfish nerve fibers incubated with radiolabeled glutamate or glutamine accumulate these substrates and synthesize radioactive N-acetylaspartylglutamate (NAAG). Upon stimulation of the medial giant nerve fiber, NAAG is the primary radioactive metabolite released. Since NAAG activates a glial hyperpolarization comparable to that initiated by glutamate or axonal stimulation through the same receptor, we have proposed that it is the likely mediator of interactions between the medial giant axon and its periaxonal glia. This manuscript reports investigations of possible mechanisms for termination of NAAG-signaling activity. N-acetylaspartyl-[3H]glutamate was not accumulated from the bath saline by unstimulated crayfish giant axons or their associated glia during a 30-min incubation. Stimulation of the central nerve cord at 50 Hz during the last minute of the incubation dramatically increased the levels of radiolabeled glutamate, NAAG, and glutamine in the medial giant axon and its associated glia. These results indicate that stimulation-sensitive peptide hydrolysis and metabolic recycling of the radiolabeled glutamate occurred. There was a β-NAAG-, quisqualate- and 2-(phosphonomethyl)-pentanedioic acid-inhibitable glutamate carboxypeptidase II activity in the membrane fraction of central nerve fibers, but not in axonal or glial cytoplasmic fractions. Inactivation of this enzyme by 2-(phosphonomethyl)-pentanedioic acid or inhibition of N-methyl-D-aspartate (NMDA) receptors by MK801 reduced the glial hyperpolarization activated by high-frequency stimulation. These results indicate that axon-to-glia signaling is terminated by NAAG hydrolysis and that the glutamate formed contributes to the glial electrical response in part via activation of NMDA receptors. Both NAAG release and an increase in glutamate carboxypeptidase II activity appear to be induced by nerve stimulation.

AB - Crayfish nerve fibers incubated with radiolabeled glutamate or glutamine accumulate these substrates and synthesize radioactive N-acetylaspartylglutamate (NAAG). Upon stimulation of the medial giant nerve fiber, NAAG is the primary radioactive metabolite released. Since NAAG activates a glial hyperpolarization comparable to that initiated by glutamate or axonal stimulation through the same receptor, we have proposed that it is the likely mediator of interactions between the medial giant axon and its periaxonal glia. This manuscript reports investigations of possible mechanisms for termination of NAAG-signaling activity. N-acetylaspartyl-[3H]glutamate was not accumulated from the bath saline by unstimulated crayfish giant axons or their associated glia during a 30-min incubation. Stimulation of the central nerve cord at 50 Hz during the last minute of the incubation dramatically increased the levels of radiolabeled glutamate, NAAG, and glutamine in the medial giant axon and its associated glia. These results indicate that stimulation-sensitive peptide hydrolysis and metabolic recycling of the radiolabeled glutamate occurred. There was a β-NAAG-, quisqualate- and 2-(phosphonomethyl)-pentanedioic acid-inhibitable glutamate carboxypeptidase II activity in the membrane fraction of central nerve fibers, but not in axonal or glial cytoplasmic fractions. Inactivation of this enzyme by 2-(phosphonomethyl)-pentanedioic acid or inhibition of N-methyl-D-aspartate (NMDA) receptors by MK801 reduced the glial hyperpolarization activated by high-frequency stimulation. These results indicate that axon-to-glia signaling is terminated by NAAG hydrolysis and that the glutamate formed contributes to the glial electrical response in part via activation of NMDA receptors. Both NAAG release and an increase in glutamate carboxypeptidase II activity appear to be induced by nerve stimulation.

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