NK1 receptors mediate the increase in mucociliary activity produced by tachykinins

The mucociliary activity of the rabbit maxillary sinus is increased after exposure to airway irritants such as cigarette smoke and capsaicin. This effect is partly due to a cholinergic reflex but involves an atropine-resistant response probably mediated by the release of tachykinins such as substance P or neurokinin A from sensory nerve endings. The aim of the present investigation was to evaluate the type of tachykinin receptor which mediates this increase in mucociliary activity. The mucociliary activity of the rabbit maxillary sinus was studied photoelectrically in vivo. It was found that a selective NK1 receptor agonist, [Sar9,Met(O2)11]substance P, dose dependently stimulated mucociliary activity, the maximum increase being 43.74 +/- 6.07% at a dose of 1 nmol/kg. A selective NK2 receptor agonist, [Nle10]neurokinin A-(4-10), produced a much weaker response, the maximum increase being 15.23 +/- 3.86% at a dose of 10 nmol/kg, whereas an NK3 receptor agonist, [Pro7]neurokinin B, was without effect. When the effects of the selective agonists were compared with the responses elicited by naturally occurring tachykinins at a dose of 1 pmol/kg, the order of the magnitude of the responses was [Sar9,Met(O2)11]substance P > substance P > neurokinin A. At this dosage the NK2 and NK3 receptor agonists did not have a significant effect. Pretreatment with the endopeptidase inhibitor phosphoramidon did not influence the magnitude of the responses but increased their duration. It is concluded that the NK1 receptor is responsible for the increase in mucociliary activity elicited by tachykinins released from sensory afferents in the upper airways.