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.
First Department of Medicine, Tokyo Women's Medical College.
J
J
Tamaoki
T
T
Kanemura
S
S
Horii
K
K
Takeyama
T
T
Takizawa
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