Pharmacological characterization of airway smooth muscle responses to antigen in ascaris-sensitive dogs

M. S. Kannan, C. Davis, A. Sankaranarayanan, A. R. Ladenius

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The dog model of ascaris airway sensitivity was chosen because of its frequency and its immunological 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: (i) tetrodotoxin-insensitive spontaneous active tone; (ii) phasic contractions of airway smooth muscle; and (iii) 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 densensitized 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.

Original languageEnglish (US)
Pages (from-to)1361-1367
Number of pages7
JournalCanadian Journal of Physiology and Pharmacology
Volume64
Issue number11
DOIs
StatePublished - Jan 1 1986

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