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Mefloquine-induced disruption of calcium homeostasis in Mammalian cells is similar to that induced by ionomycin.

Mefloquine-induced disruption of calcium homeostasis in Mammalian cells is similar to that induced by ionomycin. Research Abstract Details 

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  • Mefloquine-induced disruption of calcium homeostasis in Mammalian cells is similar to that induced by ionomycin. Abstract Text:

    d caridhaD Caridha,d yourickD Yourick,m cabezasM Cabezas,l wolfL Wolf,t h hudsonT H Hudson,g s dowG S Dow,d caridhaD Caridha,d yourickD Yourick,m cabezasM Cabezas,l wolfL Wolf,t h hudsonT H Hudson,g s dowG S Dow,

    In previous studies, we have shown that mefloquine disrupts calcium homeostasis in neurons by depletion of endoplasmic reticulum (ER) stores, followed by an influx of external calcium across the plasma membrane. In this study, we explore two hypotheses concerning the mechanism(s) of action of mefloquine. First, we investigated the possibility that mefloquine activates non-N-methyl-d-aspartic acid receptors and the inositol phosphate 3 (IP3) signaling cascade leading to ER calcium release. Second, we compared the disruptive effects of mefloquine on calcium homeostasis to those of ionomycin in neuronal and nonneuronal cells. Ionomycin is known to discharge the ER calcium store (through an undefined mechanism), which induces capacitative calcium entry (CCE). In radioligand binding assays, mefloquine showed no affinity for the known binding sites of several glutamate receptor subtypes. The pattern of neuroprotection induced by a panel of glutamate receptor antagonists was dissimilar to that of mefloquine. Both mefloquine and ionomycin exhibited dose-related and qualitatively similar disruptions of calcium homeostasis in both neurons and macrophages. The influx of external calcium was blocked by the inhibitors of CCE in a dose-related fashion. Both mefloquine and ionomycin upregulated the IP3 pathway in a manner that we interpret to be secondary to CCE. Collectively, these data suggest that mefloquine does not activate glutamate receptors and that it disrupts calcium homeostasis in mammalian cells in a manner similar to that of ionomycin.

    Mefloquine-induced disruption of calcium homeostasis in Mammalian cells is similar to that induced by ionomycin. Publishing Authors By Initials

    d caridhaD Caridha,d yourickD Yourick,m cabezasM Cabezas,l wolfL Wolf,th hudsonTH Hudson,gs dowGS Dow,d caridhaD Caridha,d yourickD Yourick,m cabezasM Cabezas,l wolfL Wolf,th hudsonTH Hudson,gs dowGS Dow,

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    Mefloquine-induced disruption of calcium homeostasis in Mammalian cells is similar to that induced by ionomycin. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Antimicrobial agents and chemotherapy

    VOLUME: 52

    Page Numbers: 684-93

    Journal Abbreviation: Antimicrob. Agents Chemother.

    ISSN: 0066-4804

    DAY: 12

    MONTH: 11

    YEAR: 2007

    Mefloquine-induced disruption of calcium homeostasis in Mammalian cells is similar to that induced by ionomycin. Information

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    LANGUAGE: eng

    NlmUniqueID: 315061

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    Grant and Affiliation Information for Mefloquine-induced disruption of calcium homeostasis in Mammalian cells is similar to that induced by ionomycin.

    AFFILIATION: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910. geoffrey.dow@na.amedd.army.mil.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Antimicrob Agents Chemother

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