Fenamates inhibit contraction of guinea-pig isolated bronchus in vitro independent of prostanoid synthesis inhibition.
The inhibitory and relaxant effects of flufenamic and tolfenamic acids on guinea-pig isolated bronchus were compared with those of verapamil and indomethacin. Flufenamic and tolfenamic acids (each drug, 20 microM) and verapamil (1 microM) inhibited bronchial contraction induced by Ca2+, KCl or PGF2alpha whereas indomethacin (20 microM) had no inhibitory effect. Only verapamil, but not flufenamic and tolfenamic acids and indomethacin, inhibited methacholine-induced contraction. Flufenamic and tolfenamic acids and verapamil (each drug, 0.1-33 microM) relaxed the bronchus precontracted by KCl or PGF2alpha. In contrast, indomethacin (0.1-33 microM) did not relax KCl- or PGF2alpha-precontracted bronchus. Verapamil, but not flufenamic and tolfenamic acids and indomethacin, relaxed methacholine precontracted bronchus. In conclusion, fenamates inhibit Ca2+-, KCl- and PGF2alpha-induced contractions in guinea-pig isolated bronchus in a manner involving inhibition of Ca2+ influx but not inhibition of prostanoid synthesis.
Li
L
L
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Vapaatalo
H
H
Vaali
K
K
Paakkari
I
I
Kankaanranta
H
H
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002118:Calcium / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005439:Flufenamic Acid / Q000494:pharmacology*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016085:Bronchoconstrictor Agents; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D014665:Vasodilator Agents; D062367:ortho-Aminobenzoates; D016210:Methacholine Chloride; C009500:tolfenamic acid; D005439:Flufenamic Acid; D014700:Verapamil; D002118:Calcium; D007213:Indomethacin