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.
D000109:Acetylcholine / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects*; D000242:Cyclic AMP / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000109:Acetylcholine; D000420:Albuterol; D009638:Norepinephrine