α- and β-adrenergic receptor activity in circulating blood cells of patients with phaeochromocytoma: effects of adrenalectomy

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Abstract
In many tissues adrenergic responsiveness may be impaired by chronic exposure to adrenergic agonists. We examined the effects of high levels of circulating norepinephrine and epinephrine to .alpha.2- and .beta.2-adrenoceptors on platelets and mononuclear leucocytes (MNL) of patients with phaeochromocytoma. When compared with controls the density of .beta.2-receptors prior to removal of the tumor was diminished by 67% (500 .+-. 160 sites/cell, n = 7 vs. 1500 .+-. 350 sites/cell, n = 29; P < 0.001). Binding affinities for [3H]dihydroalprenolol (apparent KD = 0.45 .+-. 0.16 nmol/l in phaeochromocytoma, 0.52 .+-. 0.19 nmol/l in controls) were not significantly different in MNL preparations from the two groups. MNL adenylate cyclase activities in response to 10 .mu.mol/l (-) isoproterenol was lower in the patients (7.5 vs. 22 pmol cAMP/106 MNL/10 min; P < 0.001). Conversely, the number of .alpha.2-adrenoceptors on platelets and the affinity of these receptors for [3H]yohimbine did not differ between patients and controls. Ensuing adrenalectomy the regeneration of the .beta.-adrenergic cAMP-system results from a two-phase process. A prompt but moderate restoration was followed by a gradual rise to the normal range within about 1 to 2 months indicating the dynamic character of the .beta.2-adrenoceptor cAMP-system in MNL. We conclude that the downregulation observed in MNL, which appears not to be operative in human platelets, represents only one mechanism of feedback control in the sympatho-adrenal-system protecting tissues from prolonged stimulation by excessive catecholamines.

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