The first objective is to find the site of the putative beta adrenergic defect in asthma. The human neutrophil model will be used to characterize the beta receptor, receptor coupling to the enzyme adenylate cyclase, and the activity of adenylate cyclase itself in asthmatic and control individuals. Receptor characteristics determined with the ligand dihydroalprenolol (DHA), and adenylate cyclase activity will utilize the neutrophil sonicate preparation. In addition, intact neutrophils will be assessed for beta receptor binding and function (cyclic AMP generation) and phosphodiesterase and ATPase activity will be compared in the two populations. The second objective is to determine the in vitro conditions required for desensitization of the beta adrenergic receptor, the specificity of this phenomenon and the effects of such drugs as corticosteroids and teophylline on preventing and reversing this process.
NIH ExPorter
NIH ExPorter