Alpha- and beta-adrenergic receptor activity in circulating blood cells of patients with phaeochromocytoma: effects of adrenalectomy.
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.
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
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D007545:Isoproterenol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine