Relationships between responsiveness of the bronchi to acetylcholine and cyclic AMP response of lymphocytes to beta 1- and beta 2-adrenergic receptor stimulation in patients with asthma.

Decreased response of beta-adrenergic receptor has been considered to be one of the causes of increased responsiveness of the bronchi in asthma. Since beta-adrenergic receptor has two subtypes, beta 1 and beta 2, and the bronchodilating effect of beta stimulants is mediated by beta 2-receptor, responsiveness of the bronchi is expected to correlate to the cyclic AMP response of lymphocytes to a beta 2-stimulant. Responsiveness of the bronchi was expressed as respiratory threshold to acetylcholine (RT-Ach), which was the minimal concentration of acetylcholine solution to cause an initial decrease of FEV1 of more than 20% of the baseline value. Beta 1- and beta 2-responses were expressed as the increments of cyclic AMP content of 10(6) lymphocytes incubated with norepinephrine (beta 1-stimulant) and salbutamol (beta 2-stimulant). RT-Ach showed a significant correlation with the beta 2-cyclic AMP response of lymphocytes, but not with the beta 1-response among patients with asthma. Sixteen symptomatic patients on continuous beta-stimulants showed lower RT-Ach value and diminished beta 2-receptor activity of lymphocytes compared with 14 patients in remission. These results suggest that selective beta 2-adrenergic blockade may be one of the causes of bronchial hypersensitivity in asthma, though it should be noted that in this study beta-adrenergic responses were examined in lymphocytes and were compared with the responsiveness of the bronchi. Possible beta-receptor subsensitivity induced by administration of beta-stimulants is discussed.