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Cyclothiazide modulates AMPA receptor-mediated increases in intracellular free Ca2+ and Mg2+ in cultured neurons from rat brain.
J Neurochem. 1995 May; 64(5):2049-56.JN

Abstract

We investigated the modulation of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced increases in intracellular free Ca2+ ([Ca2+]i) and intracellular free Mg2+ ([Mg2+]i) by cyclothiazide and GYKI 52466 using microspectrofluorimetry in single cultured rat brain neurons. AMPA-induced changes in [Ca2+]i were increased by 0.3-100 microM cyclothiazide, with an EC50 value of 2.40 microM and a maximum potentiation of 428% of control values. [Ca2+]i responses to glutamate in the presence of N-methyl-D-aspartate (NMDA) receptor antagonists were also potentiated by 10 microM cyclothiazide. The response to NMDA was not affected, demonstrating specificity of cyclothiazide for non-NMDA receptors. Almost all neurons responded with an increase in [Ca2+]i to both kainate and AMPA in the absence of extracellular Na+, and these Na(+)-free responses were also potentiated by cyclothiazide. GYKI 52466 inhibited responses to AMPA with an IC50 value of 12.0 microM. Ten micromolar cyclothiazide significantly decreased the potency of GYKI 52466. However, the magnitude of this decrease in potency was not consistent with a competitive interaction between the two ligands. Cyclothiazide also potentiated AMPA- and glutamate-induced increases in [Mg2+]i. These results are consistent with the ability of cyclothiazide to decrease desensitization of non-NMDA glutamate receptors and may provide the basis for the increase in non-NMDA receptor-mediated excitotoxicity produced by cyclothiazide.

Authors+Show Affiliations

Department of Pharmacology, University of Pittsburgh, PA 15216, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7536804

Citation

Hoyt, K R., et al. "Cyclothiazide Modulates AMPA Receptor-mediated Increases in Intracellular Free Ca2+ and Mg2+ in Cultured Neurons From Rat Brain." Journal of Neurochemistry, vol. 64, no. 5, 1995, pp. 2049-56.
Hoyt KR, Rajdev S, Fattman CL, et al. Cyclothiazide modulates AMPA receptor-mediated increases in intracellular free Ca2+ and Mg2+ in cultured neurons from rat brain. J Neurochem. 1995;64(5):2049-56.
Hoyt, K. R., Rajdev, S., Fattman, C. L., & Reynolds, I. J. (1995). Cyclothiazide modulates AMPA receptor-mediated increases in intracellular free Ca2+ and Mg2+ in cultured neurons from rat brain. Journal of Neurochemistry, 64(5), 2049-56.
Hoyt KR, et al. Cyclothiazide Modulates AMPA Receptor-mediated Increases in Intracellular Free Ca2+ and Mg2+ in Cultured Neurons From Rat Brain. J Neurochem. 1995;64(5):2049-56. PubMed PMID: 7536804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclothiazide modulates AMPA receptor-mediated increases in intracellular free Ca2+ and Mg2+ in cultured neurons from rat brain. AU - Hoyt,K R, AU - Rajdev,S, AU - Fattman,C L, AU - Reynolds,I J, PY - 1995/5/1/pubmed PY - 1995/5/1/medline PY - 1995/5/1/entrez SP - 2049 EP - 56 JF - Journal of neurochemistry JO - J Neurochem VL - 64 IS - 5 N2 - We investigated the modulation of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced increases in intracellular free Ca2+ ([Ca2+]i) and intracellular free Mg2+ ([Mg2+]i) by cyclothiazide and GYKI 52466 using microspectrofluorimetry in single cultured rat brain neurons. AMPA-induced changes in [Ca2+]i were increased by 0.3-100 microM cyclothiazide, with an EC50 value of 2.40 microM and a maximum potentiation of 428% of control values. [Ca2+]i responses to glutamate in the presence of N-methyl-D-aspartate (NMDA) receptor antagonists were also potentiated by 10 microM cyclothiazide. The response to NMDA was not affected, demonstrating specificity of cyclothiazide for non-NMDA receptors. Almost all neurons responded with an increase in [Ca2+]i to both kainate and AMPA in the absence of extracellular Na+, and these Na(+)-free responses were also potentiated by cyclothiazide. GYKI 52466 inhibited responses to AMPA with an IC50 value of 12.0 microM. Ten micromolar cyclothiazide significantly decreased the potency of GYKI 52466. However, the magnitude of this decrease in potency was not consistent with a competitive interaction between the two ligands. Cyclothiazide also potentiated AMPA- and glutamate-induced increases in [Mg2+]i. These results are consistent with the ability of cyclothiazide to decrease desensitization of non-NMDA glutamate receptors and may provide the basis for the increase in non-NMDA receptor-mediated excitotoxicity produced by cyclothiazide. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/7536804/Cyclothiazide_modulates_AMPA_receptor_mediated_increases_in_intracellular_free_Ca2+_and_Mg2+_in_cultured_neurons_from_rat_brain_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=1995&volume=64&issue=5&spage=2049 DB - PRIME DP - Unbound Medicine ER -