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.