Tags

Type your tag names separated by a space and hit enter

Glycine site antagonists and partial agonists inhibit N-methyl-D-aspartate receptor-mediated [3H]arachidonic acid release in cerebellar granule cells.
J Pharmacol Exp Ther. 1998 May; 285(2):527-32.JP

Abstract

Activation of N-methyl-D-aspartate (NMDA) receptors is known to produce arachidonic acid release, which has been implicated in excitotoxicity. Antagonists and partial agonists at the glycine site of the NMDA receptor, despite exhibiting functional differences in electrophysiological studies, inhibit glutamate-induced neurotoxicity and ischemia-induced neurodegeneration. The objective of this study was to investigate the effects of both glycine site antagonists and partial agonists on NMDA receptor-mediated [3H]arachidonic acid (AA) release evoked by glutamate, NMDA or a competitive inhibitor of the glutamate/aspartate uptake carrier. The [3H]AA release evoked by a maximally effective concentration of glutamate (100 microM) was blocked by the glycine site antagonists 7-chlorokynurenic acid (7-CKYN) and 5,7-dichlorokynurenic acid (5,7-DCKYN) and by a low intrinsic efficacy glycine partial agonist (+)-1-hydroxy-3-aminopyrrolid-2-one [(+)-HA-966]. 1-Aminocyclopropanecarboxylic acid (ACPC), a high intrinsic efficacy glycine partial agonist, did not modify [3H]AA release evoked by 100 microM glutamate. However, ACPC blocked (in a glycine reversible manner) the [3H]AA release induced by NMDA (100 microM) with an IC50 of 131 +/- 2 microM. Furthermore, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a competitive inhibitor of the glutamate transporter, also released [3H]AA (Emax and EC50 of 127 +/- 4% and 30 +/- 1 microM, respectively). ACPC, 7-CKYN and (+/-)-2-amino-7-phosphonoheptanoic acid (AP-7), a competitive NMDA receptor antagonist, inhibited [3H]AA release evoked by PDC. These results demonstrate that both glycine site antagonists and partial agonists can inhibit NMDA receptor-mediated [3H]AA release in cerebellar granule cells, an action consistent with the neuroprotective effects of these compounds.

Links

Publisher Full Text

Authors+Show Affiliations

Viu E
Department of Bioanalítica Mèdica, Institut d'Investigacions Biomèdiques de Barcelona, Spain.
Zapata A
No affiliation info available
Capdevila JL
No affiliation info available
Fossom LH
No affiliation info available
Skolnick P
No affiliation info available
Trullas R
No affiliation info available

MeSH

Amino AcidsAmino Acids, CyclicAnimalsArachidonic AcidCerebellumGlutamic AcidKynurenic AcidN-MethylaspartateRatsRats, WistarReceptors, GlycineReceptors, N-Methyl-D-Aspartate

Pub Type(s)

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

Language

eng

PubMed ID

9580593

Citation

Viu, E, et al. "Glycine Site Antagonists and Partial Agonists Inhibit N-methyl-D-aspartate Receptor-mediated [3H]arachidonic Acid Release in Cerebellar Granule Cells." The Journal of Pharmacology and Experimental Therapeutics, vol. 285, no. 2, 1998, pp. 527-32.
Viu E, Zapata A, Capdevila JL, et al. Glycine site antagonists and partial agonists inhibit N-methyl-D-aspartate receptor-mediated [3H]arachidonic acid release in cerebellar granule cells. J Pharmacol Exp Ther. 1998;285(2):527-32.
Viu, E., Zapata, A., Capdevila, J. L., Fossom, L. H., Skolnick, P., & Trullas, R. (1998). Glycine site antagonists and partial agonists inhibit N-methyl-D-aspartate receptor-mediated [3H]arachidonic acid release in cerebellar granule cells. The Journal of Pharmacology and Experimental Therapeutics, 285(2), 527-32.
Viu E, et al. Glycine Site Antagonists and Partial Agonists Inhibit N-methyl-D-aspartate Receptor-mediated [3H]arachidonic Acid Release in Cerebellar Granule Cells. J Pharmacol Exp Ther. 1998;285(2):527-32. PubMed PMID: 9580593.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycine site antagonists and partial agonists inhibit N-methyl-D-aspartate receptor-mediated [3H]arachidonic acid release in cerebellar granule cells. AU - Viu,E, AU - Zapata,A, AU - Capdevila,J L, AU - Fossom,L H, AU - Skolnick,P, AU - Trullas,R, PY - 1998/5/15/pubmed PY - 1998/5/15/medline PY - 1998/5/15/entrez SP - 527 EP - 32 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 285 IS - 2 N2 - Activation of N-methyl-D-aspartate (NMDA) receptors is known to produce arachidonic acid release, which has been implicated in excitotoxicity. Antagonists and partial agonists at the glycine site of the NMDA receptor, despite exhibiting functional differences in electrophysiological studies, inhibit glutamate-induced neurotoxicity and ischemia-induced neurodegeneration. The objective of this study was to investigate the effects of both glycine site antagonists and partial agonists on NMDA receptor-mediated [3H]arachidonic acid (AA) release evoked by glutamate, NMDA or a competitive inhibitor of the glutamate/aspartate uptake carrier. The [3H]AA release evoked by a maximally effective concentration of glutamate (100 microM) was blocked by the glycine site antagonists 7-chlorokynurenic acid (7-CKYN) and 5,7-dichlorokynurenic acid (5,7-DCKYN) and by a low intrinsic efficacy glycine partial agonist (+)-1-hydroxy-3-aminopyrrolid-2-one [(+)-HA-966]. 1-Aminocyclopropanecarboxylic acid (ACPC), a high intrinsic efficacy glycine partial agonist, did not modify [3H]AA release evoked by 100 microM glutamate. However, ACPC blocked (in a glycine reversible manner) the [3H]AA release induced by NMDA (100 microM) with an IC50 of 131 +/- 2 microM. Furthermore, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a competitive inhibitor of the glutamate transporter, also released [3H]AA (Emax and EC50 of 127 +/- 4% and 30 +/- 1 microM, respectively). ACPC, 7-CKYN and (+/-)-2-amino-7-phosphonoheptanoic acid (AP-7), a competitive NMDA receptor antagonist, inhibited [3H]AA release evoked by PDC. These results demonstrate that both glycine site antagonists and partial agonists can inhibit NMDA receptor-mediated [3H]AA release in cerebellar granule cells, an action consistent with the neuroprotective effects of these compounds. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9580593/Glycine_site_antagonists_and_partial_agonists_inhibit_N_methyl_D_aspartate_receptor_mediated_[3H]arachidonic_acid_release_in_cerebellar_granule_cells_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9580593 DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓4]

Related Citations

More