Pharmacological characterization of airway smooth muscle responses to antigen in ascaris-sensitive dogs.
The dog model of ascaris airway sensitivity was chosen because of its frequency and its immunologic similarity to the human atopic asthmatic state. We studied the mediators of the antigen-induced airway response in vitro and the alterations in the in vivo and in vitro responsiveness to spasmogens evoked by antigen challenge. A myogenic basis of altered reactivity was suggested by the following: tetrodotoxin-insensitive spontaneous active tone; phasic contractions of airway smooth muscle; and responsiveness to leukotrienes C4 and D4. The pharmacologic characteristics of the antigen-induced airway smooth muscle contraction in vitro were similar to those induced by arachidonic acid and the leukotrienes only in some respects but were clearly different from those induced by compound 48/80. This suggested a predominant role for arachidonate lipoxygenase products. Histamine appeared to play a minor role in the antigen response. Comparisons were made between antigen-induced responses of actively and passively sensitized airways tissues. In the latter, histamine release appeared to contribute to the initial antigen-induced contraction and, unlike in actively sensitized airways, the responses were easily desensitized to repeated challenge. Alterations of airway responsiveness were demonstrated in vivo to acetylcholine and 5-HT following antigen challenge of highly ascaris-sensitive dogs. In vitro studies of passively sensitized muscle showed selectively enhanced response to 5-HT following antigen challenge. These studies support the presence of altered myogenic properties of airway smooth muscle and nonspecific increased airway responsiveness in this animal model.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001200:Ascaris / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006967:Hypersensitivity / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000503:physiopathology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000947:Antigens, Helminth; D001095:Arachidonic Acids; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D009543:Nifedipine; D000109:Acetylcholine; D007213:Indomethacin