کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2570682 1128597 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mefenamic acid bi-directionally modulates the transient outward K+ current in rat cerebellar granule cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Mefenamic acid bi-directionally modulates the transient outward K+ current in rat cerebellar granule cells
چکیده انگلیسی

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K+ current (IA) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 μM to 100 μM, mefenamic acid reversibly inhibited IA in a dose-dependent manner. However, mefenamic acid at a concentration of 1 μM significantly increased the amplitude of IA to 113 ± 1.5% of the control. At more than 10 μM, mefenamic acid inhibited the amplitude of IA without any effect on activation or inactivation. In addition, a higher concentration of mefenamic acid induced a significant acceleration of recovery from inactivation with an increase of the peak amplitude elicited by the second test pulse. Intracellular application of mefenamic acid could significantly increase the amplitude of IA, but had no effect on the inhibition induced by extracellular mefenamic acid, implying that mefenamic acid may exert its effect from both inside and outside the ion channel. Furthermore, the activation of current induced by intracellular application of mefenamic acid was mimicked by other cyclooxygenase inhibitors and arachidonic acid. Our data demonstrate that mefenamic acid is able to bi-directionally modulate IA channels in neurons at different concentrations and by different methods of application, and two different mechanisms may be involved.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 226, Issue 3, 1 February 2008, Pages 225–235
نویسندگان
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