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    Please use this identifier to cite or link to this item: https://ir.fy.edu.tw:8080/ir/handle/987654321/9568

    Title: Inhibition of intermediate-conductance Ca2+-activated K+ channel and cytoprotective properties of 4-piperidinomethyl-2-isopropyl-5-methylphenol.
    Authors: Ai-Yu Shen;Jen-Hsiang Tsai;Hsiu-Chen Teng;Mei-Han Huang;Sheng-Nan Wu
    Contributors: 輔英科技大學 物理治療系
    Date: 2007-05-01
    Issue Date: 2010-11-10 13:32:06 (UTC+8)
    Abstract: The ionic mechanisms and cytoprotective activities of 4-piperidinomethyl-2-isopropyl-5-methylphenol (THPI), an analogue of thymol, were investigated in HL-60 granulocytes and in human erythrocytes, respectively. THPI inhibited K+ outward current (IK) in a concentration-dependent manner in HL-60 leukocytes, with an IC50 value of 4 μM. Neither iberiotoxin (200 nM) nor paxilline (1 μM) suppressed the amplitude of IK, whereas clotrimazole (5 μM) significantly inhibited it. In the inside-out configuration of single channel recordings, application of THPI (5 μM) into the bath medium did not alter the single-channel conductance of intermediate-conductance Ca2+-activated K+ (IKCa) channels (i.e KCa3.1 channels), but it suppressed the channel activity significantly. THPI-induced inhibition of IKCa channels was reversed by a further application of 1-ethyl-2-benzimidazolinone (10μM). THPI-induced reduction in IKCa-channel activity in these cells was primarily due to a decrease in mean open time. These results provide direct evidence that THPI is capable of suppressing the activity of IKCa channels in HL-60 cells. The antioxidant action of THPI also revealed a beneficial cytoprotective effect against mitomycin C-mediated haemolytic effect in human erythrocytes. The results of this study suggest that blockade of IKCa channels and the membrane-protecting activity of THPI would combine to have beneficial effects in lessening the severity of haemolytic crisis and reducing anaemia in sickle cell disease.
    Relation: J Pharm Pharmacol. 59(5),679-685
    Appears in Collections:[物理治療系] 期刊論文

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