Active alpha₂ and beta adrenoceptors in lymphocytes from patients with chronic lymphocytic leukemia

Abstract

A single population of alpha 2 adrenoceptors was characterized in intact B lymphocytes from patients with chronic lymphocytic leukemia (B-CLL) by binding and saturation studies with 3H labelled yohimbine and by competition studies with alpha adrenergic antagonists. While the affinity of B-CLL alpha 2 adrenoceptors was low (KD: 9.81 nM-20.98 nM), each cell expressed a large number of receptors. No binding of the alpha 1 adrenoceptor antagonist prazosin was observed and the binding properties of beta adrenergic receptors (assayed with 3H-labelled dihydroalprenolol), were similar to those described for normal lymphocytes. Reaction of B-CLL with the beta adrenergic agonist isoproterenol raised the levels of cAMP in 11/13 patients tested, and in 8 of these, incubation with the alpha 2 adrenergic agonist clonidine prevented the effect and reduced the basal cAMP levels. The presence of active alpha 2 adrenoceptors on B-CLL lymphocytes may be involved in the regulation of metabolic pathways that affect cell functions and favor neoplastic growth.

α 1 -Adrenergic Receptor Subtypes in Human Peripheral Blood Lymphocytes

“…This suggests that human peripheral blood lymphocyte ␣ 1 -adrenergic receptors may have functional relevance. Comparative analysis of the density of ␣ 1 -adrenergic receptors measured in this work with data reported for lymphocyte ␣ 2 -adrenergic receptors 6,7 showed a ratio of ␣ 1 -to ␣ 2 -adrenergic receptor of approximately 7.9 in human peripheral blood lymphocytes. The role of lymphocyte ␣ 1 -adrenergic receptors has not been clarified yet.…”

“…6,7 Radioligand binding studies performed with [ 3 H]prazosin were unable to identify ␣ 1 -adrenergic receptors in normal 8 or leukemic human lymphocytes 7 or reported the expression of these receptors in peripheral human natural killer cells. 10 In view of these discrepancies we have reinvestigated the topic using both molecular biology and radioligand binding assay techniques.…”

“…[1][2][3][4][5][6][7] The suitability of techniques so far proposed for demonstrating ␣-adrenergic receptor expression in normal lymphoid cells is still controversial. ␣ 2 -Adrenergic receptors were demonstrated in human peripheral blood lymphocytes using […”

“…[1][2][3][4][5] Data on the expression of ␣-adrenergic receptors in peripheral blood lymphocytes are less extensive, with the ␣ 2 -receptor subtype being the most extensively investigated. 6,7 Some studies on the ␣ 1 -adrenergic receptor have not found its expression in human peripheral blood lymphocytes 8,9 and some studies have. 10 ␣ 1 -Adrenergic receptors mediate some cardiovascular sympathetic responses, such as arteriolar smooth muscle constriction 11 and cardiac contractility, 12 and are involved in a variety of cardiovascular disorders, including hypertension, heart failure, and cardiac hypertrophy.…”

Potential clozapine target sites on peripheral hematopoietic cells and stromal cells of the bone marrow

“…20 In addition, peripheral cells such as blood lymphocytes express D2, 21 D3, 22,23 D4, 23,24 D5 receptors, 25 M2, M3, M4, M5 receptors 26,27 and a1 28 and a2 receptors 29,30 using radioligand binding studies. Since pharmacological characterization remains difficult given the lack of suitable receptor-specific ligands, 31 the expression of neurotransmitter receptors by the detection of corresponding mRNAs has recently been undertaken.…”