title: Alpha- and beta-adrenergic receptor activity in circulating blood cells of patients with phaeochromocytoma: effects of adrenalectomy.
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 tumour was diminished by 67% (500 +/- 160 sites/cell, n = 7 vs 1500 +/- 350 sites/cell, n = 29; P less than 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 mumol/l (-) isoproterenol was lower in the patients (7.5 vs 22 pmol cAMP/10(6) MNL/10 min; P less than 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.
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000097:blood*; D000315:Adrenalectomy; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D000242:Cyclic AMP / Q000097:blood; D004082:Dihydroalprenolol / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010673:Pheochromocytoma / Q000097:blood*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D007545:Isoproterenol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine