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(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.
Li
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Institute of Biomedicine, Department of Pharmacology and Toxicology, P.O. Box 8, University of Helsinki, Helsinki, Finland. liangli@ruby.iupui.edu
Vaali
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Vapaatalo
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Kankaanranta
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D005439:Flufenamic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists; D014132:Trachea / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D062367:ortho-Aminobenzoates; D019806:Cromakalim; C009500:tolfenamic acid; D005439:Flufenamic Acid; D015237:Dinoprost; D009543:Nifedipine; D007213:Indomethacin