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  • Title: Subsensitization of beta-adrenoceptors in airways and lymphocytes of healthy and asthmatic subjects.
    Author: Tashkin DP, Conolly ME, Deutsch RI, Hui KK, Littner M, Scarpace P, Abrass I.
    Journal: Am Rev Respir Dis; 1982 Feb; 125(2):185-93. PubMed ID: 6278998.
    Abstract:
    Subsensitization of beta-adrenoceptors in airways and lymphocytes developing during 4 to 5 wk of orally administered terbutaline (a long-acting beta 2 selective bronchodilator) was compared in 10 healthy subjects and 11 subjects with mild asthma. The following results were obtained. Normal subjects developed a significant reduction in acute bronchodilator responsiveness to inhaled isoproterenol but not to subcutaneously administered terbutaline. The subjects with asthma failed to develop any alteration in responsiveness to either inhaled isoproterenol or subcutaneously administered terbutaline. None of 5 normal or 4 asthmatic subjects studied demonstrated any significant change in sensitivity to histamine-induced bronchospasm or any significant decrease in the acute protective effect of subcutaneously administered terbutaline against histamine-induced bronchospasm. Marked and significant decreases occurred in the density of lymphocyte beta-receptor sites in both groups. Maximal isoproterenol-stimulated cyclic AMP responses in lymphocytes from normal subjects were reduced, but in asthmatics, in whom the baseline values were lower to begin with, a similar decrease was not observed. In most instances, the number of receptor sites returned to normal within 2 wk after cessation of terbutaline. A single dose of methylprednisolone caused a return to normal values within 16 h. We conclude that chronic therapy with an oral beta 2-adrenostimulant, although producing striking and significant down-regulation of beta-adrenergic receptors of peripheral lymphocytes, does not lead to physiologically detectable beta-adrenoceptor subsensitivity in the airways of asthmatics or to consistent subsensitivity in the airways of healthy persons.
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