Effect of the anti-asthmatic agent KC-404 on the contractile responses of rabbit airway smooth muscle to tachykinins.
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.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College.
Kanemura
T
T
Horii
S
S
Takeyama
K
K
Takizawa
T
T
D000818:Animals; D001993:Bronchodilator Agents; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D013373:Substance P / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D007212:Indolizines; D011720:Pyrazoles
D001993:Bronchodilator Agents; D015288:Neurokinin A; D011725:Pyridines; D013373:Substance P; D015320:Tachykinins; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles