Airway smooth muscle (ASM) has an abnormal behaviour in airway diseases, such as asthma, with increases in airway responsiveness following exposure to concentrations of bronchoconstrictors innocuous in a normal individual (Mauger et al., 2001). To investigate the mechanisms underlying this abnormal response of ASM to allergens, animal models are required. In particular, developing a mouse model is necessary because of the availability of transgenic and gene-targeted animals (Kumar et al., 2002). Initial studies were needed to establish the pharmacology of naïve ASM, so responses of the tracheal smooth muscle isolated from naïve male and female mice to a range of agonists were compared.

Male and female BALB/c mice, 25-30g, were kept at 19-23^oC with a 12 hour light-dark cycle and received food and water ad libitum. Animals were killed by pentobarbital sodium overdose (i.p.). The trachea was carefully dissected out, cut into a spiral (1.5-2cm) and mounted in a 20ml organ bath in Krebs-bicarbonate solution maintained at 37^oC and gassed with 5% CO₂ in O₂. Changes in isometric tension of the ASM were measured using an isometric tension transducer and recorded on a polygraph. After equilibration with a resting tension of 500mg for 60 min, tracheal preparations were contracted by the cumulative addition of carbachol, methacholine and histamine and non-cumulative addition of adenosine and 5-hydroxytryptamine (5-HT) to the organ bath (10^-8M to 10^-4M). The contractile responses of the trachea were expressed as a % of the maximal response to methacholine (10^-4M). Geometric mean EC₅₀ value and 95% confidence limits were calculated. All male and female values were compared with Students' 't' tests and one-way ANOVA (n=3-14).

Methacholine and 5-HT (male and female) and carbachol (male) produced concentration-related tracheal contractions (Table 1). Histamine did not contract the trachea, and adenosine neither contracted nor relaxed the methacholine (3x10^-7M) pre-contracted trachea in either sex. There were no significant differences between any values for male and female mice (p>0.05).

Table 1: EC₅₀ values and % of maximal response to methacholine for contractile responses in trachea from male and female mice.

This is the first study to investigate the pharmacology of the mouse trachea in detail. We have demonstrated in both sexes that cholinergic and serotoninergic pathways, but not adenosine or histaminergic pathways, are involved in mouse tracheal contraction. The cholinergic effect appears to be more important. Interestingly, mouse trachea does not respond to adenosine or histamine, unlike guinea-pig ASM which is sensitive to these agents (Martin & Broadley, 2002).

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