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Ifenprodil prevents glutamate cytotoxicity via polyamine modulatory sites of N-methyl-D-aspartate receptors in cultured cortical neurons.
J Pharmacol Exp Ther. 1993 May; 265(2):1017-25.JP

Abstract

Neuroprotective effects of ifenprodil, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, against glutamate cytotoxicity were examined in cultured rat cortical neurons. The viability of the cultures was markedly reduced by a 10-min exposure to glutamate followed by incubation with glutamate-free medium for 60 min. Ifenprodil and its derivative SL 82.0715 dose-dependently prevented cell death induced by glutamate. The NMDA antagonists MK-801 and 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid also prevented glutamate cytotoxicity with a potency similar to that of ifenprodil. Ifenprodil as well as MK-801 prevented NMDA-induced cytotoxicity, but did not affect kainate-induced cytotoxicity. Glutamate cytotoxicity was inhibited by removing extracellular Ca++ during and immediately after glutamate exposure. Ifenprodil and MK-801 reduced NMDA-induced Ca++ influx measured with rhod-2. Either spermidine, a polyamine modulatory site agonist, or glycine, a strychnine-insensitive glycine site agonist, potentiated NMDA- and glutamate-induced cytotoxicity. The protective effects of ifenprodil against NMDA- and glutamate-induced cytotoxicity were significantly reduced by spermidine, but not by glycine. These findings indicate that ifenprodil protects cortical neurons against glutamate cytotoxicity by selective antagonism of the polyamine modulatory site of the NMDA receptor complex.

Authors+Show Affiliations

Department of Neuropharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8098757

Citation

Tamura, Y, et al. "Ifenprodil Prevents Glutamate Cytotoxicity Via Polyamine Modulatory Sites of N-methyl-D-aspartate Receptors in Cultured Cortical Neurons." The Journal of Pharmacology and Experimental Therapeutics, vol. 265, no. 2, 1993, pp. 1017-25.
Tamura Y, Sato Y, Yokota T, et al. Ifenprodil prevents glutamate cytotoxicity via polyamine modulatory sites of N-methyl-D-aspartate receptors in cultured cortical neurons. J Pharmacol Exp Ther. 1993;265(2):1017-25.
Tamura, Y., Sato, Y., Yokota, T., Akaike, A., Sasa, M., & Takaori, S. (1993). Ifenprodil prevents glutamate cytotoxicity via polyamine modulatory sites of N-methyl-D-aspartate receptors in cultured cortical neurons. The Journal of Pharmacology and Experimental Therapeutics, 265(2), 1017-25.
Tamura Y, et al. Ifenprodil Prevents Glutamate Cytotoxicity Via Polyamine Modulatory Sites of N-methyl-D-aspartate Receptors in Cultured Cortical Neurons. J Pharmacol Exp Ther. 1993;265(2):1017-25. PubMed PMID: 8098757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ifenprodil prevents glutamate cytotoxicity via polyamine modulatory sites of N-methyl-D-aspartate receptors in cultured cortical neurons. AU - Tamura,Y, AU - Sato,Y, AU - Yokota,T, AU - Akaike,A, AU - Sasa,M, AU - Takaori,S, PY - 1993/5/1/pubmed PY - 1993/5/1/medline PY - 1993/5/1/entrez SP - 1017 EP - 25 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 265 IS - 2 N2 - Neuroprotective effects of ifenprodil, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, against glutamate cytotoxicity were examined in cultured rat cortical neurons. The viability of the cultures was markedly reduced by a 10-min exposure to glutamate followed by incubation with glutamate-free medium for 60 min. Ifenprodil and its derivative SL 82.0715 dose-dependently prevented cell death induced by glutamate. The NMDA antagonists MK-801 and 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid also prevented glutamate cytotoxicity with a potency similar to that of ifenprodil. Ifenprodil as well as MK-801 prevented NMDA-induced cytotoxicity, but did not affect kainate-induced cytotoxicity. Glutamate cytotoxicity was inhibited by removing extracellular Ca++ during and immediately after glutamate exposure. Ifenprodil and MK-801 reduced NMDA-induced Ca++ influx measured with rhod-2. Either spermidine, a polyamine modulatory site agonist, or glycine, a strychnine-insensitive glycine site agonist, potentiated NMDA- and glutamate-induced cytotoxicity. The protective effects of ifenprodil against NMDA- and glutamate-induced cytotoxicity were significantly reduced by spermidine, but not by glycine. These findings indicate that ifenprodil protects cortical neurons against glutamate cytotoxicity by selective antagonism of the polyamine modulatory site of the NMDA receptor complex. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8098757/Ifenprodil_prevents_glutamate_cytotoxicity_via_polyamine_modulatory_sites_of_N_methyl_D_aspartate_receptors_in_cultured_cortical_neurons_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8098757 DB - PRIME DP - Unbound Medicine ER -