Involvement of endogenous tachykinins in LTD(4)-induced airway responses

Leukotriene D-4-(LTD(4)) has been reported to cause tachykinin release from airway sensory nerves, However, the functional significance of endogenously released tachykinins in LTD(4)-mediated airway responses has not been fully clarified. The aim of this study was to investigate whether LTD(4)-induced airway responses are due, in part, to tachykinin release in guinea-pigs, Airway plasma exudation and bronchoconstriction were assessed by measuring extravasation of Evans blue dye and by mean pulmonary resistance (RL) in the presence of atropine (1 mg . kg(-1) i.v.) and propranolol (1 mg . kg(-1) iv.), respectively. LTD(4) (5 mu g . mL(-1) for 1 min) inhalation caused increase in plasma exudation and RL. Capsaicin pretreatment of animals to deplete sensory neuropeptides significantly inhibited LTD(4)-induced plasma exudation in the main bronchi, but not in the central (cIPA) and peripheral intrapulmonary airways (pIPA). Pretreatment with specific tachykinin neurokinin-1 (NK1)-receptor antagonists, FK 888 (10 mg . kg(-1) i.v.) and CP 96345 (4 mg . kg(-1) i.v.), also significantly reduced LTD(4)-induced plasma exudation in the main bronchi, and in the main bronchi and cIPA, respectively. However, these antagonists did not significantly affect the LTD(4)-induced increase in RL. In contrast, neurokinin-2 (NK2)-receptor antagonist, SR 48968 (0.3 mg . kg(-1) i.v.), significantly inhibited the bronchoconstriction after LTD(4)-inhalation. These results suggest that leukotriene D-4-induced bronchoconstriction and plasma exudation in guinea-pips are, in part, due to tachykinin release from airway sensory nerves. (C)ERS Journals Ltd 1996.