EVIDENCE THAT ALLERGEN-INDUCED CONTRACTION OF GUINEA-PIG BRONCHI IS MEDIATED IN PART BY THE RELEASE OF TACHYKININS

To study the role of tachykinins in allergic responses in the airways of guinea pigs sensitized to ovalbumin (OVA), we examined the bronchia l contractile response to allergen in the presence or absence of the t achykinin antagonist FK224 in vitro. Because neutral endopeptidase (NE P) effectively cleaves tachykinins, we incubated bronchial tissues wit h the NEP inhibitor phosphoramidon (10(-5) M) to maintain the activity of endogenously released tachykinins. Then we added 10(-5)% (10 mu g/ ml) OVA in the presence or absence of FK224 (10(-5) M). FK224 signific antly inhibited OVA-induced contraction from 25 min after the addition of OVA. In the next stages the experiment in the presence or absence of FK224, when the OVA-induced contraction plateaued and began to rela x, we added 10(-5) M phosphoramidon. In the tissue without FK224, phos phoramidon blocked the relaxation and enhanced the contraction. In con trast, in the tissues treated with FK224, phosphoramidon did not enhan ce the OVA-induced contraction. The enhancement of the contraction ind uced by phosphoramidon was not inhibited by the sodium channel blocker tetrodotoxin. These results suggest that (1) allergic response causes release of tachykinin-like substances to induce bronchial contraction in part, (2) these responses are blocked by tachykinin antagonist FK2 24 and (3) nerve conduction is not necessary for the release of tachyk inin-like substances induced by allergic response in the guinea pig br onchus.