Desensitization of the beta-adrenoceptor of lymphocytes from normal subjects and patients with phaeochromocytoma: studies in vivo.
1 Following the observation that lymphocyte beta-adrenoceptor responsiveness was not depressed in asthmatics treated only with non-adrenergic drugs we have explored the effects of prolonged exposure to beta-adrenoceptor agonists in normal subjects. 2 Treatment with oral salbutamol (12-16 mg/kg/day for 10 days), or with inhaled salbutamol (3000 microgram/day for 8-10 days) resulted in a significant reduction in lymphocyte beta-adrenoceptor responsiveness. 3 A 48 h infusion of isoxsuprine (10 mg/h) resulted in a marked depression of lymphocyte beta-adrenoceptor responsiveness (P less than 0.001). 4 Prolonged elevation of endogenous catecholamines caused by phaeochromocytoma was also associated with a marked depression of lymphocyte beta-adrenoceptor responsiveness (P less than 0.001). 5 There was no evidence that an increase in phosphodiesterase activity could explain the reduced cyclic AMP response. 6 It is concluded that diminished beta-adrenoceptor response occurs as a response to prolonged exposure to beta-adrenoceptor agonists. It is likely that the diminished response seen in asthmatic subjects can be explained on a similar basis and does not indicate an inherent cellular defect. 7 The possible clinical significance of such changes in asthmatics are discussed.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000503:physiopathology*; D000420:Albuterol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007556:Isoxsuprine / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects*; D010673:Pheochromocytoma / Q000503:physiopathology*; D011458:Prostaglandins E / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011458:Prostaglandins E; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D007545:Isoproterenol; D000420:Albuterol; D007556:Isoxsuprine