α- and β-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 \g=a\2-and \g=b\2-adrenoceptors on platelets and mononuclear leucocytes (MNL) of patients with phaeochromocytoma. When compared with controls the density of \g=b\2-receptors prior to removal of the tumour was diminished by 67% (500 \ m=+-\ 160 sites/cell, n = 7 vs 1500 \ m=+-\350 sites/cell, n = 29; P < 0.001). Binding affinities for [3H]dihydroalprenolol (apparent KD = 0.45 \m=+-\0.16 nmol/l in phaeochromocvtoma, 0.52 \m=+-\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 \g=m\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 \g=a\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 \g=b\-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 \g=b\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.It is now well established that ß-adrenergic recep¬ tor-mediated function is attenuated by chronic exposure of cells or tissues to ß-adrenergic ago¬ nists. This feedback regulation, also known for a wide variety of other hormone receptors, has been termed tachvphvlaxis or desensitization.For ß-adrenergic receptors this process includes a decreased ß-receptor mediated cyclic AMP

Direct relationship between mononuclear leukocyte and lung beta-adrenergic receptors and apparent reciprocal regulation of extravascular, but not intravascular, alpha- and beta-adrenergic receptors by the sympathochromaffin system in humans.

“…An inverse relationship between endogenous plasma catecholamine concentrations and leukocyte fl-adrenergic receptor density in normal humans has been reported (14,16), but others have not found these to be correlated (7,17,18). In patients with markedly elevated plasma catecholamine concentrations due to catecholamine-secreting pheochromocytomas, reduced leukocyte f3-adrenergic receptor density has been reported (19,20). Platelet a-adrenergic receptor density has not been found to be related to plasma catecholamine concentrations in normal humans (21,22) and has been reported to be normal (20,23) or decreased (19,24) in patients with pheochromocytomas.…”

“…In patients with markedly elevated plasma catecholamine concentrations due to catecholamine-secreting pheochromocytomas, reduced leukocyte f3-adrenergic receptor density has been reported (19,20). Platelet a-adrenergic receptor density has not been found to be related to plasma catecholamine concentrations in normal humans (21,22) and has been reported to be normal (20,23) or decreased (19,24) in patients with pheochromocytomas. Do these seemingly contradictory data indicate that adrenergic receptor down regulation by endogenous catecholamines is of little physiologic relevance in humans, or do they reflect limited utility of the use of adrenergic receptors on intravascular circulating cells as indices of the regulation of adrenergic receptors on extravascular catecholamine target tissues by the sympathochromaffin system?…”

Phaeochromocytoma without symptoms: desensitization of the ?- and ?-adrenoceptors

“…Limited information is available regarding regulation of 13-adrenoceptors in human phaeochromocytoma. Ratge and Wisser [6] and Chobanian et al [2] found a decreased density of these receptors in patients with phaeochromocytoma.…”

“…Davies et al [3], Chobanian et al [2], and Brodde and Bock [1] reported low numbers of a-adrenoceptors, whereas Snavely et al [9], Jones et al [4], and Ratge and Wisser [6] found no abnormality in the receptor density in patients with phaeochromocytoma. These contradictory results may in part be related to the use of different ligands.…”

“…This phenomenon has been termed desensitization. The regulation of a-adrenergic receptors by adrenergic agonists is less well defined [1- 4,6,9]. Limited information is available documenting the consequences of chronic in vivo exposure to catecholamines as a consequence of human phaeochromocytoma.…”