Abstract：
: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 (I(A)) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 microM to 100 microM, mefenamic acid reversibly inhibited I(A) in a dose-dependent manner. However, mefenamic acid at a concentration of 1 microM significantly increased the amplitude of I(A) to 113+/-1.5% of the control. At more than 10 microM, mefenamic acid inhibited the amplitude of I(A) 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 I(A), 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 I(A) channels in neurons at different concentrations and by different methods of application, and two different mechanisms may be involved.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Zhang M,Shi WJ,Fei XW,Liu YR,Zeng XM,Mei YAdoi
10.1016/j.taap.2007.09.008subject
Has Abstractpub_date
2008-02-01 00:00:00pages
225-35issue
3eissn
0041-008Xissn
1096-0333pii
S0041-008X(07)00417-6journal_volume
226pub_type
杂志文章abstract：:Chronic exposure to high concentrations of arsenic in drinking water is associated with an increased risk for developing type 2 diabetes. The present revision focuses on the effect of arsenic on tissues that participate directly in glucose homeostasis, integrating the most important published information about the imp...
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