Involvement of capsaicin-sensitive afferent neurones in a vagal-dependent interaction between leukotriene D4 and histamine on bronchomotor tone

Abstract

Leukotriene D₄ (LTD₄, 0.1–0.5 μg/kg, i.v.), administered 20 s before histamine (H, 1–4 μg/kg, i.v.), enhanced the bronchoconstrictor response to H by between 105 and 168%. Bilateral vagotomy, atropine or indomethacin each attenuated, whereas hexamethonium completely prevented, this enhancement. LTD₄ failed to enhance the bronchoconstrictor effects of either acetylcholine (ACh) or electrical stimulation of the vagi. Capsaicin pretreatment reduced bronchoconstrictor responses to electrical stimulation of the vagi, but did not affect depressor responses. There was no interaction between LTD₄ and H on bronchomotor tone in capsaicin-pretreated guinea-pigs. It is concluded that LTD₄ enhances H-induced bronchoconstriction by a mechanism which involves an increased activity of efferent cholinergic nerves innervating the airways. However, the failure of LTD₄ to enhance bronchoconstriction due to ACh or vagal stimulation, together with the prevention of the interaction between LTD₄ and H by capsaicin-pretreatment, suggests that the site of the interaction may be on capsaicin-sensitive afferent neurones.