PHARMACOLOGY OF SCHULTZ‐DALE REACTION IN CANINE LUNG STRIP in vitro: POSSIBLE MODEL FOR ALLERGIC ASTHMA

Abstract

1 Isolated lung parenchymal strips of the dog contracted in response to histamine > carbachol > prostaglandin F_2α (PGF_2α) > bradykinin (Bk) > 5-hydroxytryptamine (5-HT). The order of the relative activity of these agents on the tracheobronchial smooth muscles (TBSM) was carbachol > 5-HT > histamine; PGF_2α and Bk were inactive. Thus there are marked differences in the responsiveness of the smooth muscle of central (trachea and bronchus) and peripheral (lung strip) airways to autonomic and autacoid agents. 2 Lung strips and TBSM partially contracted by carbachol, histamine or horse plasma, were relaxed by isoprenaline, PGE₁ and PGE₂. 3 Lung strips from dogs sensitized to horse-plasma contracted in response to antigen (Schultz-Dale anaphylactic reaction). Tachyphylaxis or desensitization to subsequent antigen challenge was invariably observed; it was followed after 1 to 2 h of rest by partial recovery of the anaphylactic response. 4 Mepyramine selectively antagonized responses to histamine without altering responses to carbachol and antigen. 5 Metiamide, an H₂-receptor antagonist, did not influence responses to histamine, carbachol or horse plasma. 6 Indomethacin was found to be ineffective as an inhibitor of the Schultz-Dale anaphylactic reaction. 7 The results showed the presence of H₁-histamine receptors mediating constriction in the peripheral airways of the dog. Histamine and PGF_2α appear to have no important role in the anaphylactic reaction in this tissue. The involvement of slow reacting substance of anaphylaxis (SRS-A) and endoperoxides (thromboxanes) in allergic reactions of canine lung is strongly suggested.