Dynamics of the lymphocyte beta-adrenoceptor system in patients with allergic bronchial asthma.
It has been proposed that reduced beta-adrenergic responsiveness plays an important role in the increased airway reactivity of asthmatic patients. This hypothesis has been supported by studies showing reduced beta-adrenergic responsiveness in lymphocytes of asthmatic patients, predominantly during the occurrence of active and severe symptoms. Little is known about the mechanism underlying this relationship and its clinical relevance with respect to bronchial hyperreactivity. Therefore, in this study we assessed the status of the beta-adrenergic receptor-adenylate cyclase system in lymphocytes of allergic asthmatic patients in relation to parameters of bronchial hyperreactivity. This was performed before and after challenge with house-dust mite allergen, as a possible modulating factor of beta-adrenergic responsiveness. It was shown that lymphocytes of 'stable' allergic asthmatic patients with increased airway reactivity may have normal beta-adrenergic responsiveness and a normal beta-adrenergic receptor number. After allergen challenge, however, a group of 12 patients developed reduced beta-adrenergic responsiveness, which could be partially attributed to changes in the beta-adrenergic receptor number, while changes distal to the receptor also occurred. The results indicate that reduced beta-adrenergic responsiveness in lymphocytes of allergic asthmatic patients is a consequence of an active disease state rather than the reflection of a primary aetiological factor. A number of the patients concomitantly developed enhanced bronchial reactivity to propranolol after allergen challenge, which might indicate that reduced beta-adrenergic receptor function also occurs at the level of the bronchial tree. In five of the patients it was shown that beta-adrenergic hyporesponsiveness could be restored after environmental control in combination with drug treatment, thus indicating the dynamic character of the lymphocyte beta-adrenergic receptor system in asthmatic patients.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D002462:Cell Membrane / Q000201:enzymology; D004082:Dihydroalprenolol / Q000494:pharmacology; D005260:Female; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000201:enzymology / Q000276:immunology*; D008297:Male; D011433:Propranolol / Q000009:adverse effects; D011943:Receptors, Adrenergic, beta / Q000503:physiopathology*; D012130:Respiratory Hypersensitivity / Q000276:immunology
D011943:Receptors, Adrenergic, beta; D006153:Guanosine Diphosphate; D004082:Dihydroalprenolol; D006160:Guanosine Triphosphate; D011433:Propranolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol