dinoprost and tolfenamic-acid

The effects of different K(+) channel inhibitors on flufenamic- and tolfenamic-acids-induced relaxation were studied in prostaglandin F(2alpha) (1 microM) precontracted guinea-pig trachea. Flufenamic and tolfenamic acids (each 0.1-33 microM) and lemakalim (0.01-33 microM), but not indomethacin (0.1-33 microM), 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 microM)-induced relaxation. Nifedipine (0.1 microM) inhibited the blockade of fenamate-induced relaxation by iberiotoxin. Apamin (0.1 and 1 microM) did not affect flufenamic- and tolfenamic-acids- and lemakalim-induced relaxation. Glibenclamide (10 and 33 microM) 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 Ca(2+)-activated K(+) channels and differs from that of lemakalim.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcium Channel Blockers; Calcium Channels, L-Type; Cromakalim; Dinoprost; Female; Flufenamic Acid; Guinea Pigs; In Vitro Techniques; Indomethacin; Male; Muscle Relaxation; Nifedipine; ortho-Aminobenzoates; Potassium Channel Blockers; Potassium Channels; Trachea

The effects of K+ channel inhibitors on the relaxations induced by flufenamic and tolfenamic acids and lemakalim were examined in guinea-pig isolated trachea precontracted with prostaglandin F2alpha (PGF2alpha, 1 microM). Flufenamic and tolfenamic acids (0.1-33 microM) and lemakalim (0.01-33 microM) relaxed guinea-pig trachea in a concentration-dependent manner. Tetraethylammonium (0.5-2 mM), a nonspecific inhibitor of K+ channels, inhibited the relaxations induced by flufenamic and tolfenamic acids without affecting lemakalim-induced relaxation. Charybdotoxin (ChTX, 33-100 nM), an inhibitor of the large Ca2+-activated K+ channels (BK(Ca)), also inhibited the relaxations induced by flufenamic and tolfenamic acids without affecting lemakalim-induced relaxation. Glipizide (3.3-33 microM), an inhibitor of the ATP-sensitive K+ channels (K(ATP)) inhibited lemakalim-induced relaxation without affecting those induced by flufenamic and tolfenamic acids. Our results indicate that the relaxations of guinea-pig isolated trachea by flufenamic and tolfenamic acids are due to activation of BK(Ca). The relaxant mechanism of flufenamic and tolfenamic acids thus differs from that of lemakalim, an activator of K(ATP).

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchodilator Agents; Charybdotoxin; Cromakalim; Dinoprost; Dose-Response Relationship, Drug; Female; Flufenamic Acid; Glipizide; Guinea Pigs; Large-Conductance Calcium-Activated Potassium Channels; Male; Muscle Relaxation; Muscle, Smooth; ortho-Aminobenzoates; Potassium Channel Blockers; Potassium Channels; Potassium Channels, Calcium-Activated; Tetraethylammonium; Trachea