The beta-adrenergic system and allergic bronchial asthma: changes in lymphocyte beta-adrenergic receptor number and adenylate cyclase activity after an allergen-induced asthmatic attack

Abstract

Beta-adrenergic receptor characteristics and adenylate cyclase responses to different stimuli were measured in lymphocyte membrane preparations of six normal control subjects and five allergic asthmatic patients with mild airways disease and increased bronchial reactivity to histamine and acetylcholine. The determinations were performed just before and 24 hr after inhalation challenge with house-dust mite antigen to investigate the influence of an allergen-induced asthmatic attack on the beta-adrenergic receptor system. Before the house-dust mite challenge, the lymphocyte membranes of the patients showed a normal receptor density, dissociation constant for (−) 3H-dihydroalprenolol, and adenylate cyclase response to isoproterenol, guanyl-5′-yl-imidodiphosphate, (GppNHp) and NaF. After the allergen-induced asthmatic reaction, however, the beta-adrenergic receptor number in the patients was significantly reduced by 21%, while the basal adenylate cyclase activity and isoproterenol-, GppNHp-, and NaF-induced cyclic AMP responses were simultaneously reduced by about 40%. The allergen challenge had no significant effect on the lymphocyte membranes of the control subjects. These results suggest (1) that a reduced beta-adrenergic function is not an intrinsic component of allergic bronchial asthma but is rather the consequence of an active disease state, and (2) that next to changes in beta-adrenergic receptor number, alterations distal to the receptor may play an important role in the observed decrease in beta-adrenergic responsiveness.