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Effect of the anti-asthmatic agent KC-404 on the contractile responses of rabbit airway smooth muscle to tachykinins

Effect of the anti-asthmatic agent KC-404 on the contractile responses of rabbit airway smooth muscle to tachykinins

Arerugi 39(2 Pt 1): 99-103

To characterize the antagonistic action of KC-404, an anti-asthmatic agent, against the tachykinin-mediated bronchoconstriction, we studied the effect of this drug on the contractile responses of rabbit tracheal smooth muscle to neurokinin A (NKA) and substance P (SP) under isometric conditions in vitro. Addition of KC-404 relaxed the tracheal rings precontracted with NKA and SP in a dose-dependent fashion but had only a small effect on the contractile responses to acetylcholine and histamine. This inhibitory action of KC-404 was likewise noted even in the presence of atropine. In addition, each of NKA and SP at a concentration insufficient to alter the resting tone enhanced the contractile response to electrical filed stimulation, an effect that was dose-dependently attenuated by the subsequent application of KC-404. These results suggest that KC-404 may antagonize the bronchoconstrictor actions of tachykinins by interacting with their specific receptors on smooth muscle cells as well as on cholinergic nerve terminals in the airway.

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Accession: 039944158

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PMID: 1693847

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