Tachykinins activate guinea-pig alveolar macrophages: Involvement of NK₂ and NK₁ receptors

1. The effects of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were evaluated on superoxide anion production by guinea-pig alveolar macrophages (AM). 2. SP dose-dependently (ED₅₀ = 0.7 nM) evoked superoxide anion production from guinea-pig AM; the N-terminal heptapeptide, SP(1-7), was ineffective. In the presence of thiorphan (10^-5 M), an enkephalinase inhibitor, the stimulating effects of SP were not significantly modified. NKA and KNB were both able to induce superoxide anion production from guinea-pig AM, ED₅₀ values being 0.1 and 1.3 nM, respectively. Therefore, the rank order of activity of natural tachykinins was NKA > SP > NKB. Tachykinin-evoked effects were quantitatively similar to those elicited by the autacoid mediator PAF-acether and less than those induced by the synthetic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). 3. The NK₂ receptor agonist [β-Ala⁸]-NKA (4-10) dose-dependently evoked superoxide anion production from guinea-pig AM; the NK₁ receptor agonist [Pro⁹]-SP sulphone acted only at high concentrations, while the NK₃ receptor agonist [Me,Phe⁷]-NKB was ineffective. 4. These findings indicate that guinea-pig AM possess NK₂ and possibly some NK₁ tachykinin receptors and further suggest tachykinin involvement in lung pathophysiology.