Effects of K+ channel inhibitors on relaxation induced by flufenamic and tolfenamic acids in guinea-pig trachea

The effects of different K+ channel inhibitors on flufenamic- and tolfenamic-acids-induced relaxation were studied in prostaglandin F-2 alpha (1 mu M) precontracted guinea-pig trachea. Flufenamic and tolfenamic acids (each 0.1-33 mu M) and lemakalim (0.01-33 mu M), but not indomethacin (0.1-33 mu M), caused relaxation. Iberiotoxin (33 and 100 nM) inhibited flufenamic- and tolfenamic-acids-, but not lemakalim-, induced relaxation. Iberiotoxin (100 nM) inhibited nifedipine (10 nM-10 mu M)-induced relaxation. Nifedipine (0.1 mu M) inhibited the blockade of fenamate-induced relaxation by iberiotoxin. Apamin (0.1 and 1 mu M) did not affect flufenamic- and tolfenamic-acids- and lemakalim-induced relaxation. Glibenclamide (10 and 33 mu M) inhibited lemakalim-, but not flufenamic- and tolfenamic-acids-, induced relaxation. 4-Aminopyridine (0.5 and 2 mM) inhibited flufenamic- and tolfenamic-acids- and lemakalim-induced relaxation. Flufenamic- and tolfenamic-acids-induced relaxation is likely to be activation of Ca2+-activated K+ channels and differs from that of lemakalim. (C) 1999 Elsevier Science B.V. All rights reserved.