PMID: 7536804May 1, 1995Paper

Cyclothiazide modulates AMPA receptor-mediated increases in intracellular free Ca2+ and Mg2+ in cultured neurons from rat brain

Journal of Neurochemistry
K R HoytI J Reynolds

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-induce...Continue Reading

Citations

Aug 27, 2010·Journal of Neuroscience Research·Yutaka ShindoKotaro Oka
Apr 2, 2013·Journal of Psychiatric Research·Harald Murck
Jan 1, 1997·Brain Research Bulletin·G CebersS Liljequist
May 13, 1999·Progress in Neurobiology·E Fedele, M Raiteri
Jun 30, 2001·Japanese Journal of Pharmacology·N KönigJ M Exbrayat

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