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    Please use this identifier to cite or link to this item: https://ir.fy.edu.tw:8080/ir/handle/987654321/6543

    Title: Inhibition of Ca2+-activated and voltage-dependent K+ currents by 2-mercaptophenyl-1,4-naphthoquinone in pituitary GH3 cells : Contribution to its antiproliferative effect
    Authors: Mei-Han Huang;Sheng-Nan Wu;Chi-Pien Chen;Ai-Yu Shen
    Contributors: 輔英科技大學 醫學檢驗生物技術系
    Date: 2002-01-01
    Issue Date: 2010-10-13 11:01:12 (UTC+8)
    Abstract: Quinones have been shown to possess antineoplastic activity; however, their effects on ionic currents remain unclear. The effects of 2-mercaptophenyl-1,4-naphthoquinone (2-MPNQ), menadione (MD) and 1,4-naphthoquinone (1,4NQ) on cell proliferation and ionic currents in pituitary GH3 lactotrophs were investigated in this study. 2-MPNQ was more potent than menadione or 1,4-naphthoquinone in inhibiting the growth of GH3 cells. 2-MPNQ decreased cell proliferation in a concentration-dependent manner with an IC50 value of 3 μM. In whole-cell recording experiments, 2-MPNQ reversibly caused an inhibition of Ca2+-activated K+ current (IK(Ca)) in a concentration-dependent manner. The IC50 value for 2-MPNQ-induced inhibition of IK(Ca) was 7 μM. In the inside-out configuration of single channel recording, 2-MPNQ (30 μM) applied intracellularly suppressed the activity of large-conductance Ca2+-activated K+ (BKCa) channels but did not modify single channel conductance. Menadione (30 μM) had no effect on the channel activity, whereas 1,4-naphthoquinone (30 μM) suppressed it by about 26%. Both 2-MPNQ and thimerosal suppressed the dithiothreitol-stimulated channel activity. 2-MPNQ also blocked voltage-dependent K+ currents, but it produced a slight reduction of L-type Ca2+ inward current. However, unlike E-4031, 2-MPNQ (30 μM) did not suppress inwardly rectifying K current present in GH, cells. Under the current clamp configuration, the presence of 2-MPNQ (30 μM) depolarized the cells, and increased the frequency and duration of spontaneous action potentials. The 2-MPNQ-mediated inhibition of K+ currents would affect hormone secretion and cell excitability. The blockade of these ionic channels by 2-MPNQ may partly explain its inhibitory effect on the proliferation of GH3 cells.
    Relation: Life Sci. 70(10),1185-1203
    Appears in Collections:[醫學檢驗生物技術系] 期刊論文

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