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GMP prevents excitotoxicity mediated by NMDA receptor activation but not by reversal activity of glutamate transporters in rat hippocampal slices.
Brain Res. 2008 Sep 22; 1231:113-20.BR

Abstract

Glutamate is the main excitatory neurotransmitter in the mammalian nervous system and is essential for its normal functions. However, overstimulation of glutamatergic system due to hyperactivation of NMDA receptors and/or impairment of glutamate reuptake system has been implicated in many acute and chronic neurological diseases. Regulation of extracellular glutamate concentrations relies on the function of glutamate transporters which can be reversed in situations related to excitotoxicity. Guanosine-5'-monophosphate (GMP), a guanine nucleotide which displays important extracellular roles, such as trophic effects to neurons and astrocytes, behaves as antagonist of glutamate receptors and is neuroprotective in hippocampal slices against excitotoxicity or ischemic conditions. Hippocampal slices exposed to 1 or 10 mM glutamate, or 100 microM NMDA with 10 microM glycine for 1 h and evaluated after 6 or 18 h, showed reduced cell viability and DNA fragmentation, respectively. Glutamate- or NMDA-induced cell death was prevented by 50 microM MK-801, but only NMDA-induced cell damage was prevented by GMP (1 mM). Glutamate-induced cell viability impairment and glutamate-induced l-[(3)H]glutamate release were both prevented by adding DL-TBOA (10 microM). Otherwise, NMDA-induced cell viability loss was not prevented by 10 microM of DL-TBOA and NMDA did not induce l-[(3)H]glutamate release. Our results demonstrate that GMP is neuroprotective when acting selectively at NMDA receptors. Glutamate-induced hippocampal slice damage and glutamate release were blocked by glutamate transporter inhibitor, indicating that glutamate-induced toxicity also involves the reversal of glutamate uptake, which cannot be prevented by GMP.

Authors+Show Affiliations

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18655777

Citation

Molz, Simone, et al. "GMP Prevents Excitotoxicity Mediated By NMDA Receptor Activation but Not By Reversal Activity of Glutamate Transporters in Rat Hippocampal Slices." Brain Research, vol. 1231, 2008, pp. 113-20.
Molz S, Tharine DC, Decker H, et al. GMP prevents excitotoxicity mediated by NMDA receptor activation but not by reversal activity of glutamate transporters in rat hippocampal slices. Brain Res. 2008;1231:113-20.
Molz, S., Tharine, D. C., Decker, H., & Tasca, C. I. (2008). GMP prevents excitotoxicity mediated by NMDA receptor activation but not by reversal activity of glutamate transporters in rat hippocampal slices. Brain Research, 1231, 113-20. https://doi.org/10.1016/j.brainres.2008.07.009
Molz S, et al. GMP Prevents Excitotoxicity Mediated By NMDA Receptor Activation but Not By Reversal Activity of Glutamate Transporters in Rat Hippocampal Slices. Brain Res. 2008 Sep 22;1231:113-20. PubMed PMID: 18655777.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GMP prevents excitotoxicity mediated by NMDA receptor activation but not by reversal activity of glutamate transporters in rat hippocampal slices. AU - Molz,Simone, AU - Tharine,Dal-Cim, AU - Decker,Helena, AU - Tasca,Carla I, Y1 - 2008/07/11/ PY - 2008/03/07/received PY - 2008/07/02/revised PY - 2008/07/02/accepted PY - 2008/7/29/pubmed PY - 2009/1/8/medline PY - 2008/7/29/entrez SP - 113 EP - 20 JF - Brain research JO - Brain Res VL - 1231 N2 - Glutamate is the main excitatory neurotransmitter in the mammalian nervous system and is essential for its normal functions. However, overstimulation of glutamatergic system due to hyperactivation of NMDA receptors and/or impairment of glutamate reuptake system has been implicated in many acute and chronic neurological diseases. Regulation of extracellular glutamate concentrations relies on the function of glutamate transporters which can be reversed in situations related to excitotoxicity. Guanosine-5'-monophosphate (GMP), a guanine nucleotide which displays important extracellular roles, such as trophic effects to neurons and astrocytes, behaves as antagonist of glutamate receptors and is neuroprotective in hippocampal slices against excitotoxicity or ischemic conditions. Hippocampal slices exposed to 1 or 10 mM glutamate, or 100 microM NMDA with 10 microM glycine for 1 h and evaluated after 6 or 18 h, showed reduced cell viability and DNA fragmentation, respectively. Glutamate- or NMDA-induced cell death was prevented by 50 microM MK-801, but only NMDA-induced cell damage was prevented by GMP (1 mM). Glutamate-induced cell viability impairment and glutamate-induced l-[(3)H]glutamate release were both prevented by adding DL-TBOA (10 microM). Otherwise, NMDA-induced cell viability loss was not prevented by 10 microM of DL-TBOA and NMDA did not induce l-[(3)H]glutamate release. Our results demonstrate that GMP is neuroprotective when acting selectively at NMDA receptors. Glutamate-induced hippocampal slice damage and glutamate release were blocked by glutamate transporter inhibitor, indicating that glutamate-induced toxicity also involves the reversal of glutamate uptake, which cannot be prevented by GMP. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/18655777/GMP_prevents_excitotoxicity_mediated_by_NMDA_receptor_activation_but_not_by_reversal_activity_of_glutamate_transporters_in_rat_hippocampal_slices_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(08)01668-5 DB - PRIME DP - Unbound Medicine ER -