EFFECTS OF ACTINOMYCIN-D ON AIRWAY CONSTRICTION INDUCED BY TACHYKININS AND CAPSAICIN IN GUINEA-PIGS

The effects of actinomycin D on airway constriction induced by tachykinins was studied in guinea-pigs in vitro and in vivo. Actinomycin D significantly inhibited the constriction of isolated guinea-pig trachea induced by neurokinin A (NKA) and eledoisin. Conversely, substance P (SP)- and physalaemine-induced constrictions were not affected by actinomycin D. The same selectivity in the inhibitory action of actinomycin D against tachykinins was also observed in in vivo. Actinomycin D given i.v. specifically inhibited the increase in airway resistance induced by NKA. I.v. injection of NKA caused not only airway constriction but also transient systemic hypotension. Interestingly, actinomycin D injected i.v. inhibited only airway constriction and the systemic hypotension induced by NKA was not affected. These results clearly suggest that actinomycin D specifically inhibits NKA-induced airway constriction in guinea-pigs. Actinomycin D also had an inhibitory action on the airway constriction induced by capsaicin. In the case of capsaicin-induced constriction, actinomycin D was more effective on the later phase of constriction than on the acute phase. The airway constriction induced by capsaicin is thought to be mediated by the release of SP and NKA from sensory nerve endings, and the persistent increase in airway resistance induced by capsaicin is thought to be due mainly to NKA.