Comparative effects of niflumic acid and nifedipine on 5-hydroxytryptamine- and acetylcholine-induced contraction of the rat trachea

The effects of niflumic acid, an inhibitor of Ca2+ activated Cl- (Cl-(Ca)) channels, were compared with those of the voltage-dependent Ca2+ channel (V DCC) blocker nifedipine on 5-hydroxytryptamine (5-HT)- and acetylcholine-in duced contractions of the rat isolated trachea. Niflumic acid (3-100 mu M) induced a concentration-dependent inhibition of 5-HT (10 mu M)-induced cont ractions, with a reduction to 37.0 +/- 9.5% of the control at the highest c oncentration. One micromolar nifedipine, which completely blocked 60 mM KCl -induced contractions, reduced the response to 5-HT similarly to 39.2 +/- 1 1.5% of the control. The inhibition of the 5-HT response was not significan tly different from that produced by the combined presence of nifedipine (1 mu M) and niflumic acid (100 mu M), suggesting that their effects were not additive. In contrast, neither niflumic acid (3-100 mu M) nor nifedipine (1 mu M) inhibited acetylcholine-induced contractions. The contraction to 5-H T (10 mu M) in Cl--free solution was decreased by more than similar to 85% of the control, whilst that of acetylcholine was reduced only by similar to 36%. Our data show that niflumic acid exerts selective inhibitory effects on 5-HT-induced contraction, and suggest that activation of Cl-(Ca) channel s may be a mechanism whereby 5-HT (but not acetylcholine) induces Ca2+ entr y via VDCCs to elicit contraction. (C) 2000 Published by Elsevier Science B .V. All rights reserved.