Studies on the role of arachidonic acid metabolites in airways contraction induced in vitro by antigen and calcium ionophore A23187.
The effects of inhibitors of the cyclooxygenase and lipoxygenase pathways of arachidonic acid (AA) metabolism were studied on the contractions of guinea pig tracheal spirals and lung parenchymal strips induced by antigen and calcium ionophore A23187. Inhibition of the cyclooxygenase pathway with indomethacin results in enhancement of antigen- and A23187-induced contraction of trachea which is a result of diversion of AA into the lipoxygenase pathway and inhibition of modulatory cyclooxygenase products. Indomethacin does not enhance parenchymal contractions but partly inhibits contraction induced by a strong stimulus (5.7 microM A23187 or 100 micrograms/ml ovalbumin). Parenchymal contraction is inhibited by agents that block the lipoxygenase pathway of AA metabolism, phenidone and nordihydroguaiaretic acid. These agents inhibit the prolonged phase of antigen-induced tracheal contraction but in some cases enhance the early phase of tracheal contraction induced by antigen or A23187. The results suggest that contraction of parenchyma induced by antigen or A23187 are the result of a bronchoconstrictor lipoxygenase product and only have a cyclooxygenase bronchoconstrictor component following a strong stimulus. In contrast, contraction of trachea also appears to be the result of a bronchoconstrictor lipoxygenase product which may not be identical to that contracting parenchyma, and is modulated by cyclooxygenase products. The results emphasize the importance of comparing small and large airways to further our understanding of asthmatic broncho-constriction.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D011720:Pyrazoles / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000941:Antigens; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D016718:Arachidonic Acid; D000001:Calcimycin; D010047:Ovalbumin; C015429:phenidone