CHARACTERIZATION OF ADENYLATE-CYCLASE ACTIVITY IN ASTHMATIC NEUTROPHIL SONICATES

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Abstract
Bronchial asthma is associated with a defect of the .beta.-adrenergic receptor. Previous studies using intact neutrophil (polymorphonuclear) preparations have shown decreased cyclic[c]AMP responses to isoproterenol and histamine in active bronchial asthma. Normal numbers and affinity of .beta.-adrenergic receptors were reported in homogenates of .beta.-adrenergic antagonist[3H-dihydroalprenolol]-treated polymorphonuclear leukocytes from patients with bronchial asthma. Polymorphonuclear sonicates from 25 patients with bronchial asthma and 23 normal control subjects were used to assess several steps distal to receptor binding, including adenylate cyclase coupling to the .beta.-adrenergic receptor and adenylate cyclase catalytic activity after hormonal (isoproterenol, histamine and prostaglandin E1) and NaF stimulation. The mean .+-. SEM concentration of isoproterenol that displaced 50% 3H-dihydroalprenolol (KD) was 2.31 .+-. 0.33 .mu.M for the asthmatic subjects and 3.13 .+-. 0.53 .mu.M for the control subjects. The isoproterenol concentrations that stimulated 50% maximal adenylate cyclase activity (Kact) were 0.65 .+-. 0.12 .mu.M and 0.56 .+-. 0.08 .mu.M, respectively. The adenylate cyclase coupling efficiencies (KD/Kact) of 7.50 .+-. 2.30 and 9.20 .+-. 3.00 for asthmatic and control subjects, respectively, were not significantly different (P > 0.05). The catalytic response of adenylate cyclase, in terms of Kact and net generation of cAMP after hormonal stimulation with isoproterenol, histamine and prostaglandin E1, also revealed no significant differences between the 2 populations. The unexpected basal adenylate cyclase activity of 67.3 .+-. 4.2 pmol/mg per min and the NaF stimulation of 253.0 .+-. 12.4 pmol/mg per min were significantly (P < 0.05) higher in the asthmatic group than the control group, whose corresponding values were 53.4 .+-. 4.1 pmol/mg per min and 210.3 .+-. 12.1 pmol/mg per min for basal and NaF-stimulated adenylate cyclase activity, respectively. No decreased adenylate cyclase responses were found, regardless of the asthmatic subject''s age, or sex, or the severity, activity or type of asthma involved. If the intact asthmatic polymorphonuclear leukocyte is hyporesponsive to hormone-induced generation of cAMP, this is not due to defective adenylate cyclase.

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