INVOLVEMENT OF NEUROGENIC INFLAMMATION IN ANTIGEN-INDUCED BRONCHOCONSTRICTION IN GUINEA-PIGS

The role of tachykinins released from sensory nerves in bronchoconstri ction induced by antigen was studied in sensitized guinea pigs anesthe tized with pentobarbital sodium and pretreated with atropine. The comb ination of NK2 (SR-48968) and NK1 (CP-96,345) tachykinin-receptor anta gonists abolished the increase in total pulmonary resistance (RL) evok ed by intravenous capsaicin but did not affect the response evoked by intravenous histamine. A small dose of aerosolized ovalbumin (OVA, 0.1 %) produced a small increase in RL that was further increased and mark edly prolonged by the neutral endopeptidase (NEP) inhibitor phosphoram idon; this bronchoconstrictor effect of OVA was markedly reduced by th e NK2-receptor antagonist and was abolished by the combination of the NK1 and NK2-receptor antagonists together. When a larger dose of OVA ( 0.5%) was used, a maximal bronchonconstrictor response was obtained. P hosphoramidon did not potentiate this response significantly. The comb ination of NK1- and NK2-receptor antagonists blunted the response at 5 min only slightly but markedly attenuated the later (10-20 min) respo nse. These results show that tachykinins released from sensory nerves play a significant role in antigen-induced bronchoconstriction in guin ea pigs. This effect is exaggerated when the normal modulation of neur opeptides by NEP is inhibited and is mediated predominantly by NK2-rec eptor activation, with a smaller contribution by NK1 receptors.