Flufenamic and tolfenamic acids and lemakalim relax guinea-pig isolated trachea by different mechanisms.
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).
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Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Vapaatalo
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Vaali
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Paakkari
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Kankaanranta
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology*; D005913:Glipizide / Q000494:pharmacology; D006168:Guinea Pigs; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D024681:Potassium Channels, Calcium-Activated; D019789:Tetraethylammonium / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001993:Bronchodilator Agents; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D062367:ortho-Aminobenzoates; D019806:Cromakalim; D018999:Charybdotoxin; C009500:tolfenamic acid; D005439:Flufenamic Acid; D019789:Tetraethylammonium; D015237:Dinoprost; D005913:Glipizide