N-Acetylaspartylglutamate (NAAG) is the probable mediator of axon-to-glia signaling in the crayfish medial giant nerve fiber

Gafurov, Boris; Urazaev, A. Kh.; Grossfeld, Robert M.; Lieberman, Edward M.

doi:10.1016/s0306-4522(01)00271-8

Cited by 24 publications

(38 citation statements)

References 34 publications

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“…Concurrently, radio- labeled NAAG appeared in the extracellular solution at approximately three times its pre-stimulation value by the 3rd min following stimulation. These results are consistent with the concept that NAAG might be an axonĝ lia signaling agent and/or a source of signaling glutamate (described in the following article by Gafurov et al, 2001). The decrease in concentration of glial NAAG seen following stimulation could result from changes in metabolism or indirectly from stimulation-induced glial swelling previously described in cray¢sh nerve ¢bers Hassan and Lieberman, 1988).…”

Section: Discussionsupporting

confidence: 91%

“…In unstimulated nerve ¢bers, radioactive NAAG was a major metabolic product of glutamate and was found in the extracellular solution in as large a concentration as radioactive glutamate and all other glutamate metabolic products combined. This ¢nding and the ¢nding by Gafurov et al (2001) that NAAG is a potent activator of glial hyperpolarization led us to investigate NAAG metabolism and distribution further. Despite the fact that NAAG is one of the most abundant peptides in vertebrate CNS, a possible source of neurotransmitter glutamate, and a putative neurotransmitter in its own right (Coyle, 1997;Neale et al, 2000), much uncertainty remains about its metabolism and role in nervous system function (Baslow, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…The major premises of this investigation derive from the ¢ndings that: (a) communication between giant invertebrate axons and their associated glia is essential for maintenance of adaxonal space ion homeostasis and preservation of nervous system electrical signaling (Lieberman et al, 1994); (b) communication between axons and glia in non-synaptic regions of the nervous system is mediated by agonists of both N-methyl-Daspartate (NMDA) and non-NMDA glutamate receptors (Villegas, 1978;Lieberman et al, 1989;Evans et al, 1992;Lieberman and Sanzenbacher, 1992;Villegas, 1995;Gafurov et al, 2001); and (c) the axon^glia signaling agent is released during action potential generation in proportion to the product of action potential frequency and stimulation time (Lieberman et al, 1989;Gafurov et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…In the ¢rst systematic study of the role of NAAG in axon-to-glia signaling (Gafurov et al, 2001), we have demonstrated that NAAG application to cray¢sh MGNFs hyperpolarized the associated glial cells, comparable to the e¡ect of L-glutamate on squid and cray¢sh glial cells (Evans et al, 1992;Lieberman et al, 1994). The actions of NAAG, glutamate and stimulation were shown to be mediated by Group II metabotropic glutamate receptors.…”

mentioning

confidence: 91%

“…A more recent investigation from our laboratories suggests that N-acetylaspartylglutamate (NAAG), rather than glutamate, is the probable mediator of axon^glia signaling, and that its hydrolysis is the indirect source of glutamate in the adaxonal space (Gafurov et al, 2001). The investigations described in this and the next paper were undertaken to further elucidate the role of NAAG in axon-to-glia signaling and the mechanism of appearance of extracellular glutamate following action potential generation in the cray¢sh medial giant nerve ¢ber (MGNF).…”

mentioning

confidence: 99%

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Synthesis and release of N-acetylaspartylglutamate (NAAG) by crayfish nerve fibers: implications for axon–glia signaling

et al. 2001

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

mentioning

confidence: 99%

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Synthesis and release of N-acetylaspartylglutamate (NAAG) by crayfish nerve fibers: implications for axon–glia signaling

et al. 2001

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Mechanism of NMDA receptor contribution to axon‐to‐glia signaling in the crayfish medial giant nerve fiber

Gafurov

Urazaev

Grossfeld

et al. 2002

Glia

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Electrical stimulation of crayfish giant axons at high frequency activates group II metabotropic and NMDA glutamate receptors on adjacent glial cells via release of N-acetylaspartylglutamate and glutamate formed upon its hydrolysis. This produces a transient depolarization followed by a prolonged hyperpolarization of glial cells that involves nicotinic acetylcholine receptor activation. The hyperpolarization is nearly completely blocked by antagonists of metabotropic glutamate receptors but only slightly reduced by inhibition of NMDA receptors. We report that the NMDA-induced hyperpolarization of glial cells is reduced by decreased calcium in the solution bathing the giant nerve fiber, while removal of sodium ions or block of voltage-dependent calcium channels completely prevents the glial response to NMDA. Inhibition of nicotinic acetylcholine receptors or removal of extracellular Cl(-) converts the glial response from a hyperpolarization to a depolarization that is sensitive to NMDA receptor antagonist. We propose that NMDA receptor activation by glutamate, formed from extracellular N-acetylaspartylglutamate during nerve stimulation, contributes to glial hyperpolarization by increasing intracellular Ca(2+) via opening of voltage-sensitive Ca(2+) channels. Based on our previous work, we propose further that the added Ca(2+) supplements that produced by N-acetylaspartylglutamate and glutamate acting on group II metabotropic glutamate receptors to cause an increased release of acetylcholine and a larger hyperpolarization.

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Involvement of adenylate cyclase and tyrosine kinase signaling pathways in response of crayfish stretch receptor neuron and satellite glia cell to photodynamic treatment

Uzdensky

Kolosov

Bragin

et al. 2004

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Neuroglial interactions are most profound during development or damage of nerve tissue. We studied the responses of crayfish stretch receptor neurons (SRN) and satellite glial cells to photosensitization with sulfonated aluminum phthalocyanine Photosens. Although Photosens was localized mainly in the glial envelope, neurons were very sensitive to photodynamic treatment. Photosensitization gradually inhibited and then abolished neuron activity. Neuronal and glial nuclei shrank. Some neurons and glial cells lost the integrity of the plasma membrane and died through necrosis after the treatment. The nuclei of other glial cells but not neurons become fragmented, indicating apoptosis. The number of glial nuclei around neuron soma increased, probably indicating proliferation for enhanced neuron protection. Adenylate cyclase (AC) inhibition by MDL-12330A, or tyrosine kinase (TK) inhibition by genistein, shortened neuron lifetime, whereas AC activation by forskolin or protein tyrosine phosphatases (PTP) inhibition by sodium orthovanadate prolonged neuronal activity. Therefore, cAMP and phosphotyrosines produced by AC and TK, respectively, protected SRN against photoinactivation. AC inhibition reduced photodamage of the plasma membrane and subsequent necrosis in neuronal and glial cells. AC activation prevented apoptosis in photosensitized glial cells and stimulated glial proliferation. TK inhibition protected neurons but not glia against photoinduced membrane permeabilization and subsequent necrosis whereas PTP inhibition more strongly protected glial cells. Therefore, both signaling pathways involving cAMP and phosphotyrosines might contribute to the maintenance of neuronal activity and the integrity of the neuronal and glial plasma membranes. Adenylate cyclase but not phosphotyrosine signaling pathways modulated glial apoptosis and proliferation under photooxidative stress.

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N-Acetylaspartylglutamate (NAAG) is the probable mediator of axon-to-glia signaling in the crayfish medial giant nerve fiber

Cited by 24 publications

References 34 publications

Synthesis and release of N-acetylaspartylglutamate (NAAG) by crayfish nerve fibers: implications for axon–glia signaling

Synthesis and release of N-acetylaspartylglutamate (NAAG) by crayfish nerve fibers: implications for axon–glia signaling

Mechanism of NMDA receptor contribution to axon‐to‐glia signaling in the crayfish medial giant nerve fiber

Involvement of adenylate cyclase and tyrosine kinase signaling pathways in response of crayfish stretch receptor neuron and satellite glia cell to photodynamic treatment

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