期刊
NEUROCHEMICAL RESEARCH
卷 34, 期 10, 页码 1738-1747出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-009-9983-y
关键词
Glutamate transporters; Glycine transporters; Niflumic acid; Flufenamic acid; Mefenamic acid
资金
- Australian Government National Health
- Medical Research Council
- University of Sydney
Three fenamates-niflumic, flufenamic and mefenamic acids-were tested for effects on substrate-induced currents of glutamate and glycine transporters (EAAT1, EAAT2, GLYT1b and GLYT2a) expressed in Xenopus laevis oocytes. All fenamates inhibited EAAT1 currents; 100 mu M flufenamic acid produced the most inhibition, decreasing the I (max) by 53 +/- A 4% (P < 0.001). EAAT2 currents were less sensitive, but 100 mu M flufenamic acid inhibited the I (max) by 34 +/- A 5% (P = 0.006). All fenamates inhibited GLYT1b currents; 100 mu M flufenamic acid produced the most inhibition, decreasing the I (max) by 61 +/- A 1% (P < 0.001). At 100 mu M, effects on the GLYT2a I (max) were mixed: 13 +/- A 2% inhibition by flufenamic acid (P = 0.002), 30 +/- A 6% enhancement by niflumic acid (P = 0.002), and no effect by mefenamic acid. Minor effects on substrate affinity suggested non-competitive mechanisms. These data could contribute to the development of selective transport modulators.
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