Enhanced responsiveness of ovalbumin‐sensitized guinea‐pig alveolar macrophages to tachykinins

We have evaluated the ability of substance P (SP), neurokinin A (NKA) and the selective NK₂ receptor agonist [β‐Ala⁸]‐NKA(4–10) to induce superoxide anion (O₂⁻) production and prostanoid (prostaglandin E₂, thromboxane B₂) release from alveolar macrophages (AMs) isolated from control or actively sensitized guinea‐pigs. The dose‐response curves for NKA and SP were shifted to the left (three orders and one order of magnitude, respectively) in AMs isolated from sensitized animals, with no variation in maximal effects. By evaluating the effects of [β‐Ala⁸]‐NKA(4–10), we observed that not only was the concentration‐response curve shifted to the left in both the functional parameters examined, but also maximal effects were significantly enhanced in AMs isolated from sensitized guinea‐pigs. This varied responsiveness seems to be specific for tachykinins, as it was not reproduced by another AM stimulant, the bacterial peptide N‐formylmethionyl‐leucyl‐phenylalanine (fMLP). Only small amounts of β‐glucuronidase were released following tachykinin or ovalbumin stimulation both in control and sensitized AMs. These results indicate that AMs isolated from sensitized guinea‐pigs show an increased responsiveness to NK₂ receptor stimulation and further stress the role played by AMs in allergic lung diseases. 1992 British Pharmacological Society