α ₁ -Adrenergic Receptor Subtypes in Human Peripheral Blood Lymphocytes

Abstract

Abstract-We investigated the expression of ␣ 1 -adrenergic receptor subtypes in intact human peripheral blood lymphocytes using reverse transcription-polymerase chain reaction (RT-PCR) and radioligand binding assay techniques combined with antibodies against the three subtypes of ␣ 1 -adrenergic receptors (␣ 1A , ␣ 1B , and ␣ 1D 3 H]prazosin binding to a different extent. This indicates that human peripheral blood lymphocytes express the three ␣ 1 -adrenergic receptor subtypes. Of the three different ␣ 1 -adrenergic receptor subtypes, the ␣ 1B is the most represented and the ␣ 1D , the least. Future studies should clarify the functional relevance of ␣ 1 -adrenergic receptors expressed by peripheral blood lymphocytes. The identification of these sites may represent a step for evaluating whether they represent a marker of ␣ 1 -adrenergic receptors in cardiovascular disorders or for assessing responses to drug treatment on these receptors. (Hypertension. 1999;33:708-712.) Key Words: lymphocytes Ⅲ receptors, adrenergic, alpha Ⅲ receptor subtypes Ⅲ receptor antibodies I n the past few years, ␣-and ␤-adrenergic receptors have been demonstrated in peripheral blood lymphocytes with the use of radioligand binding assay techniques. The majority of information is available on ␤-adrenergic receptors, which were investigated primarily in essential hypertension, impaired left ventricular function, and acute stress. 1-5 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. 13 ␣ 1 -Adrenergic receptors represent a class of heterogeneous receptors. 14 Cloning studies have identified three distinct ␣ 1 -adrenergic receptor subtypes, named ␣ 1a -, ␣ 1b -, and ␣ 1d -adrenergic receptors. 14 -17 At present, ␣ 1 -adrenergic receptor subtypes are defined as ␣ 1A (␣ 1a ), ␣ 1B (␣ 1b ), and ␣ 1D (␣ 1d ), with uppercase and lowercase subscripts being used to designate native or recombinant receptor, respectively. 14,18 In view of the difficulty of investigating ␣ 1 -adrenergic receptors in vivo or in vitro using human samples of cardiovascular system, circulating blood cells may represent a model for the study of the cardiovascular ␣ 1 -adrenergic receptor system.In this article we have characterized ␣ 1 -adrenergic receptor subtypes expressed by human peripheral blood lymphocytes by reverse transcription-polymerase chain reaction (RT-PCR) to detect mRNA expression and by radioligand binding assay techniques combined with antibodies against different subtypes of ␣ 1 -adrenergic receptors. Methods Subjec...

Differential Regulation of the Cell-Surface Targeting and Function of β- and α1-Adrenergic Receptors by Rab1 GTPase in Cardiac Myocytes

“…Cell-surface expression of ␤-AR and ␣ 1 -AR in neonatal cardiomyocytes was measured by intact cell ligand binding as described previously (McLean et al, 1999;Ricci et al, 1999;Calls et al, 2000) with modifications. Myocytes were cultured on 12-well plates at a density of 5 ϫ 10 5 cells/well and infected for 48 h. The myocytes were then incubated with the ligand [ 3 H]CGP12177 at a concentration of 20 nM for 2 h or with [7-methoxy-3 H]prazosin at a concentration of 10 nM for 90 min at room temperature.…”

Biophysical Characterization and Expression Analysis of Kv1.3 Potassium Channel in Primary Human Leukemic B Cells

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

“…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. 28,[32][33][34] If neurotransmitter receptors to which clozapine shows moderate to high affinity binding are found on peripheral white blood cells particularly the neutrophil and those of the bone marrow stroma, it remains possible that agranulocytosis may be related to pharmacological effects of the drug or its metabolites in susceptible individuals. In addition, the profiling of neurotransmitter receptors in these cells may enable the modulatory effect of clozapine to be examined.…”