Niflumic and flufenamic acids are potent inhibitors of chloride secretion in mammalian airway.
Effects of niflumic acid (NFA) and flufenamic acid (FFA), the two nonsteroid anti-inflammatory agents recently reported to inhibit Cl- current in Xenopus oocytes, were examined in cultured monolayers of dog and cow trachea. Both agents showed potent inhibition to the short-circuit current (Isc), an index of magnitude of transepithelial Cl- secretion, with values of Ki of 0.02 (for NFA) and 0.06 (for FFA) mM, respectively. The sensitivity sequence of Isc to the Cl- channel inhibitors tested was NFA > FFA > diphenylamine-2-carboxylate (DPC) >> anthracene-9-carboxylate (A9C). Thus, NFA and FFA are so far the most potent commercially available Cl- channel inhibitors tested in Cl(-)-secreting epithelia. The sensitivity sequence of 36Cl uptake to the above Cl- channel inhibitors in Xenopus laevis oocytes was found to be identical to the cultures of trachea. This seems to imply that the membrane Cl- channels of Xenopus oocytes are functionally similar to that identified in mammalian Cl(-)-secreting epithelia.
Chao
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Department of Physiology, University of California, San Francisco 94143-0130.
Mochizuki
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D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005439:Flufenamic Acid / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D009544:Niflumic Acid / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism; D014982:Xenopus laevis
D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D009544:Niflumic Acid; D005439:Flufenamic Acid