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 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 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 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.