Significant Role of Peptide Leukotrienes (p-LTs) in the Antigen-Induced Contractions of Human and Guinea Pig Lung Parenchymas and Bronchi or Tracheas In Vitro

Abstract

Chemical mediators responsible for the antigen-induced contractions of isolated, passively sensitized human and guinea pig lung parenchymas and bronchi or tracheas were evaluated by several antagonists and enzyme inhibitors, with emphasis on the effects of the potent and selective peptide leukotriene (p-LT) antagonist MCI-826. All of these preparations showed long-lasting contractions in response to an antigen challenge which lasted for more than 60 min. In either the human lung parenchyma and bronchus or guinea pig lung parenchyma, pretreatment with 10−6 g/ml (2.4 × 10−6M) MCI-826 significantly inhibited the late phase at 10 to 60 min after the challenge of the contraction following slight suppression of the early phase. The early phase contractions of these preparations were moderately antagonized by 10−6 g/ml mepyramine, but the late phases were not influenced or even rather enhanced. The combination treatment of MCI-826 with mepyramine additionally and markedly inhibited both phases of these preparations. On the other hand, although mepyramine apparently inhibited the early phase of the guinea pig tracheal contraction but not the late phase, no synergistic inhibitions of the contraction were observed when it was combined with MCI-826. The p-LT antagonist FPL 55712, atropine and indomethacin at 10−6 g/ml either slightly inhibited or enhanced the contractions of human lung parenchymas, guinea pig tracheas and lung parenchymas, but the effects were not significant. From these results, it should be emphasized that p-LTs largely contribute to induction of the anaphylactic contractions of human lung parenchymas as well as human bronchi and guinea pig lung parenchymas but not guinea pig tracheas.