Reversible Decrease of Surface ß₂-Adrenoceptor Number and Response in Lymphocytes of Patients with Pheochromocytoma

Abstract

To study the effect of chronic exposure to elevated plasma catecholamines on surface beta 2-adrenoceptor density, we measured these receptors in the lymphocytes of 9 patients with pheochromocytoma as well as in 27 healthy control subjects. Binding experiments were performed on intact lymphocytes using the hydrophilic ligand [3H]-CGP12177. Lymphocyte beta 2-adrenergic response was also measured in three patients. beta 2-adrenoceptor density (p < 0.01), and isoproterenol-stimulated increase in cAMP were reduced in patients with pheochromocytoma. Both parameters normalized (p < 0.05) when patients were reevaluated 4 weeks after tumor removal, coinciding with normalization of plasma epinephrine (r = -0.95, p < 0.01) and to log of plasma norepinephrine (r = -0.58, p < 0.05) in patients. We conclude that chronic catecholamine excess induces a decrease of lymphocyte beta 2-adrenoceptor surface number and response that is reversible upon normalization of plasma catecholamine levels. This regulation is mainly dependent on plasma levels of the hormone epinephrine, but norepinephrine may also play a regulatory role at supraphysiological levels.

Impaired catecholaminergic signalling of B lymphocytes in patients with chronic rheumatic diseases

“…A long term increase of catecholamines decreases β2R density through the stimulation of the β adrenoceptor kinase 2223 However, the differential regulation of β2R on CD4+ and CD8+ lymphocyte subsets in patients with RA argues against a simple down regulation of β2R due to an increase of systemic catecholamine concentrations,7 as can be seen in patients with pheochromocytoma 24. Moreover, a correlation with plasma catecholamine levels could not be shown either for systemic disease activity or for β2R density on PBMC in patients with RA 6…”

The association between norepinephrine and metabolism in patients with major depression

“…Direct effects of p-NE stimulation of β 2 -receptors on T-lymphocytes include altered T cell proliferation, T-cell differentiation, cytokine production and Thelper-cell mediated antibody production (Sanders, 2012). Furthermore, the density of lymphocyte surface β 2 -receptors has been shown to be reversibly decreased in patients with chronic catecholamine excess (Cases et al, 1995). An inverse relation between hsCRP and the generation of basal nitric oxide links elevated levels of hsCRP to endothelial dysfunction and possibly cardiac disease (Cleland et al, 2000).…”

Profound bradycardia associated with NIV removal

“…Cases et al. showed down-regulation of beta-2 receptors on lymphocytes in humans with phaeochromacytoma, which reverted to normal within four-weeks of tumour removal 6 . Ratge et al.…”