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 (O2-.) production by guinea-pig alveolar macrophages (AM). 2. SP dose-dependently (ED50 = 0.7 nM) evoked O2-. 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 NKB were both able to induce O2-. 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 greater than SP greater than 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 [beta-Ala8]-NKA (4-10) dose-dependently evoked O2-. 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.