Drug-induced changes of adenylate cyclase activity in cells from asthmatic and nonasthmatic subjects.
Monolayers of adherent mononuclear leukocytes prepared from normal subjects and asthmatic children whose bronchodilater therapy did not include sympathomimetic drugs, respond to relatively low concentrations of isoproterenol (ISO) and prostaglandin E1 with increased intracellular cyclic adenosine monophosphate (cAMP) levels. The magnitude of in vitro responses to ISO is decreased by previous contact of the cells with ISO or other, orally effective, adrenergic drugs. The desensitization is rapid, concentration- and time-dependent, and is readily reversible after removal of the desensitizing drug. The phenomenon exhibits pharmacologic specificity. Cells in which the response to restimulation with ISO was decreased exhibited full sensitivity to prostaglandin E1. No differences in these behaviors were detected in cells from normal or asthmatic subjects. The results suggest that earlier observations reporting decreased responses to beta adrenergic stimulation in asthmatics may have been due to the treatment of these patients with sympathomimetic agents and not caused by a disease-related beta adrenergic receptor dysfunction.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D002648:Child; D000242:Cyclic AMP / Q000096:biosynthesis; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013726:Terbutaline / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D011458:Prostaglandins E; D011943:Receptors, Adrenergic, beta; D013806:Theophylline; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013726:Terbutaline