The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function.
beta-Adrenoceptor function has been compared in lymphocytes of normal subjects, asthmatic patients taking large doses of beta-adrenergic bronchodilators, and comparable asthmatics treated exclusively with nonadrenergic medication. The effect of prolonged administration of beta-adrenoceptor agonists on receptor function in normal subjects has also been examined. beta-receptor response in each situation was quantitated by changes in levels of cyclic AMP, measured by a protein-binding assay. Dose response curves to isoproterenol (10 nM-0.1 mM) have been constructed for each group. Maximal increase in cyclic AMP in lymphocytes from normal subjects (393.2+/-44.0%) and in asthmatics on nonadrenergic preparations (408.3+/-46.7%) was significantly greater (P less than 0.001) than in asthmatics taking large doses of beta-sympathomimetics (67.5+/-24.2%). Depression of the cyclic AMP response appeared to correlate with the degree of exposure to beta-adrenergic agonists but not with the prevailing severity of the patient's asthma. Withdrawal of beta-adrenergic drugs was followed by a reversion of the cyclic AMP response to normal values, which suggests that the depression was drug-induced rather than an inherent feature of the disease. This interpretation was confirmed by the finding that prolonged exposure of normal subjects to high doses of a beta-adrenergic agonist caused a marked and significant (p less than 0.001) reduction in the cyclic AMP response, very similar to that seen in asthmatics on large doses of adrenergic bronchodilators. A possible link between drug-induced changes in the cyclic AMP response and the rise in the United Kingdom asthma death rate in the 1960's is discussed.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D000242:Cyclic AMP / Q000032:analysis; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology / Q000627:therapeutic use; D008214:Lymphocytes / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D007545:Isoproterenol; D000420:Albuterol