{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T17:25:23Z","timestamp":1770398723009,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,1,20]],"date-time":"2006-01-20T00:00:00Z","timestamp":1137715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\n\t\t\t\t\t<\/jats:bold> It is well known that \u03b2\u2010adrenoceptor agonists (\u03b2\u2010agonists) cause relaxation in airway smooth muscle mediated by a reduction in the concentration of intracellular Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>). However, little is currently known regarding whether reduced sensitization to Ca<jats:sup>2+<\/jats:sup> is involved in the \u03b2\u2010adrenergic relaxation.<\/jats:p><jats:p><jats:bold>Objective\n\t\t\t\t\t<\/jats:bold> This study was designed to determine the intracellular mechanisms underlying suppression of Ca<jats:sup>2+<\/jats:sup> sensitization in \u03b2\u2010adrenergic relaxation (Ca<jats:sup>2+<\/jats:sup>\u2010independent relaxation by \u03b2\u2010agonists).<\/jats:p><jats:p><jats:bold>Methods\n\t\t\t\t\t<\/jats:bold> Isometric tension and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> were simultaneously measured in fura\u20102\u2010loaded strips isolated from guinea\u2010pig tracheal smooth muscles. The relationships between tension and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> were examined in the inhibitory action of isoprenaline (ISO) and other cAMP\u2010related agents against methacholine\u2010induced contraction.<\/jats:p><jats:p><jats:bold>Results\n\t\t\t\t\t<\/jats:bold> The concentration\u2010inhibition curve for ISO against methacholine in tension was significantly dissociated from the curve for ISO in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. In ISO\u2010induced relaxation, a reduction in tension was significantly greater than that in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i.<\/jats:sub> This phenomenon was mimicked by other cAMP\u2010related agents: forskolin and dibutyryl\u2010cAMP. In contrast, the inhibitory action of SKF\u201096365, a non\u2010selective inhibitor of Ca<jats:sup>2+<\/jats:sup> channels, was associated with that in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. In the presence of Rp\u2010cAMPS, an inhibitor of protein kinase A (PKA), ISO caused an equivalent relaxation with less reduction in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. The effects of ISO were not affected by Y\u201027632, an inhibitor of Rho\u2010kinase, or by bisindolylmaleimide, an inhibitor of protein kinase C. ISO failed to inhibit contraction elicited by calyculin A, an inhibitor of myosin phosphatase.<\/jats:p><jats:p><jats:bold>Conclusion\n\t\t\t\t\t<\/jats:bold> \u03b2\u2010Adrenergic action antagonizes not only Ca<jats:sup>2+<\/jats:sup> mobilization but also Ca<jats:sup>2+<\/jats:sup> sensitization in methacholine\u2010induced contraction. The cAMP\/PKA\u2010independent, G<jats:sub>s<\/jats:sub>\u2010direct action is more potent in Ca<jats:sup>2+<\/jats:sup>\u2010independent relaxation by \u03b2\u2010agonists than the cAMP\/PKA\u2010dependent pathway. Moreover, myosin phosphatase is a fundamentally affected protein in the reduced response to Ca<jats:sup>2+<\/jats:sup> mediated by \u03b2\u2010agonist. Our results may provide evidence that this Ca<jats:sup>2+<\/jats:sup> desensitization is a novel target for a reliever medication using rapid\u2010acting \u03b2\u2010agonists in acute asthma management.<\/jats:p>","DOI":"10.1111\/j.1365-2222.2006.02412.x","type":"journal-article","created":{"date-parts":[[2006,1,20]],"date-time":"2006-01-20T17:55:14Z","timestamp":1137779714000},"page":"183-191","source":"Crossref","is-referenced-by-count":35,"title":["Involvement of reduced sensitivity to Ca<sup>2+<\/sup> in \u03b2\u2010adrenergic action on airway smooth 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