β₁-Adrenoceptors mediate smooth muscle relaxation in mouse isolated trachea

The relaxant effects to the β-adrenoceptor agonists isoprenaline, adrenaline, noradrenaline, RO363, procaterol and fenoterol were investigated in carbachol-contracted mouse isolated tracheal preparations. The order of potencies for those β-adrenoceptor agonists that induced full relaxation of carbachol-contracted mouse tracheal preparations was isoprenaline > RO363 > noradrenaline = adrenaline > fenoterol. The EC₅₀ value of isoprenaline for relaxation was 46 nM. The β₁-adrenoceptor-selective agonist, RO363, was ten times more potent than the β₂-adrenoceptor-selective agonist, fenoterol. The highly β₂-adrenoceptor-selective agonist procaterol was a partial relaxant and induced only 28 ± 4% relaxation. Relaxations induced by noradrenaline and isoprenaline were not significantly affected by the neuronal uptake inhibitor, cocaine (10 μM) or by the extraneuronal uptake inhibitor, deoxycorticosterone acetate (25 μM) respectively. The α-adrenoceptor agonist methoxamine induced no observable elevation of mouse tracheal smooth muscle tone. Schild plots for the β-adrenoceptor antagonists, atenolol and betaxolol (β₁-adrenoceptor-selective) and ICI 118,551 (β₂-adrenoceptor-selective) were linear, with slope values approaching unity. Mean pA₂ values derived for atenolol, betaxolol and ICI 118,551 for antagonism of β-adrenoceptor-mediated relaxation were 7.1, 8.4 and 7.2, respectively. These data were independent of the use of isoprenaline or noradrenaline as the agonist. These findings indicate that β-adrenoceptor-mediated relaxations of mouse isolated trachea occur predominantly through activation of β₁-adrenoceptors.