Effects of Compound 48/80 and Formyl-Methionyl-Leucyl-Phenylalanine on Isolated Guinea Pig Airways

Abstract

Compound 48/80 [4-methoxy-N-Methylbenzenethamine-formaldehyde product] and formyl-methionyl-leucyl-phenylalanine (fMLP), but not concanavalin A and dextran, contract isolated guinea pig tracheal spirals and lung parenchymal strips. fMLP induced a brief histamine-independent contraction of parenchymal strips. Tracheal contraction by fMLP was only observed in the presence of indomethacin, suggesting the involvement of a bronchostrictor lipoxygenase product of arachidonic acid (AA). Contractions induced by compound 48/80 were prolonged, were not dependent on extracellular Ca and were partly inhibited in the first 10 min by mepyramine, and after this by phenidone. Indomethacin enhanced contractions of trachea but inhibited contractions of parenchyma. Histamine only contributes to the early part of compound 48/80-induced airway contractions, and lipoxygenase-derived AA products contribute after that. Bronchoconstrictor cyclooxengenase products may also contribute to parenchymal contractions. Compound 48/80 contracts the airways in a similar manner to antigen and may provide a useful model to examine mediator release and airway smooth muscle contraction.