β1-Adrenoceptors mediate smooth muscle relaxation in mouse isolated trachea

P. J. Henry, R. G. Goldie

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    37 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)131-135
    Number of pages5
    JournalBritish Journal of Pharmacology
    Volume99
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 1990

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