Mechanisms of histamine-induced contraction of canine airway smooth muscle

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Abstract
Effects of atropine (10-10 to 10-6 M), tetrodotoxin (TTX) (10-6 g/ml) and neostigmine (10-7 M) on the histamine dose-reponse curve of canine tracheal smooth muscle (TSM) were studied in vitro. Pretreatment with atropine or TTX reduced base-line tension in some TSM samples; neostigmine invariably caused contraction of TSM. All concentrations of atropine reduced the maximum isometric tension produced by histamine (Tmax). With 10-6, 10-8 and 10-10 M atropine, Tmax was 57, 74 and 88%, respectively, of its value in paired control samples. Atropine, 10-9 to 10-6 M, increased the concentration of histamine which produced 20% of Tmax; 10-6 M also increased the concentration required to produce 50% Tmax. TTX reduced tension produced by low concentrations of histamine but had no effect at higher concentrations. Neostigmine shifted the histamine dose-response curve and caused greater tension for any given histamine concentration; Tmax increased by 30% (P < 0.05). The data are consistent with spontaneous release of acetylcholine from cholinergic nerves in the airway tissue and suggest that histamine accelerates this release or interacts supra-additively with the acetylcholine at the smooth muscle.