Antigen-induced contraction of guinea pig isolated pulmonary arteries and lung parenchyma.
We characterized the kinetics of and determined the mediators involved in antigen-induced contraction of pulmonary arteries (PA) and lung parenchyma isolated from actively sensitized guinea pigs. Ovalbumin (10(-2) mg/ml) induced contractions of PA rings, which reached maximum amplitude by 2 min and decayed to 50% of maximum by 4-6 min. Pyrilamine (10(-6) M) delayed the onset of contraction and decreased the peak of the response by > 50%. Metiamide (10(-4) M) partially reversed this effect. The addition of indomethacin (10(-6) M) to the combination of pyrilamine and metiamide had no significant effect. The further addition of the leukotriene (LT) D4/LTE4 receptor antagonist SKF 104353 (10(-5) M) reduced the contraction by > 80%. The maximum amplitude of antigen-induced contraction of parenchymal strips was reached by 15 min and was sustained for > 60 min. In these tissues, SKF 104353 inhibited the contraction by approximately 35%, but the histamine receptor antagonists and indomethacin had no significant effect. These results suggest that both histamine and sulfidopeptide LTs mediate antigen-induced contraction of PA, whereas sulfidopeptide LTs, but not histamine, are involved in the parenchymal response.
School of Medicine, Johns Hopkins University, Baltimore, Maryland 21239.
L J
LJ
Kelly
B J
BJ
Undem
G K
GK
Adams
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008297:Male; D008785:Metiamide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011651:Pulmonary Artery / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011738:Pyrilamine / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects / Q000276:immunology
D000941:Antigens; D003998:Dicarboxylic Acids; D013189:SRS-A; D008785:Metiamide; D010047:Ovalbumin; D011738:Pyrilamine; C052393:pobilukast; D007213:Indomethacin