ABSTRACT
Changes in the activity of ß2-adrenergic receptors of human T-lymphocytes under the effect of salbutamol (a short-acting ß2-agonist) have been evaluated with a new modified radioligand method utilizing [^(125)I]cyanopindolol and a specific ligand ICI 118551. In healthy volunteers, the receptor activity decreased after 30 min upon the inhalation of salbutamol and restored to the initial level after 2 h. At the same time, there were changes in the transcription level of the ADRB2 gene, which encodes the protein component of the ß2-adrenoreceptor. The dynamics of ß2-adrenergic receptor activity of T-lymphocytes after salbutamol treatment in patients with cardiorespiratory pathology significantly differed from that in healthy volunteers.
Subject(s)
Adrenergic beta-2 Receptor Agonists/administration & dosage , Albuterol/administration & dosage , Receptors, Adrenergic, beta-2/metabolism , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/metabolism , Aged , Aged, 80 and over , Female , Humans , Hypertension/drug therapy , Hypertension/metabolism , Male , Middle Aged , Respiratory Tract Diseases/drug therapy , Respiratory Tract Diseases/metabolismABSTRACT
According to current knowledge, autoantibodies against 1-adrenergic receptors may be involved in pathogenesis of different cardiovascular diseases and are mostly studied in patients with Chagas disease, dilated cardiomyopathy and heart rhythm disorders. They may play an important role in cardiomyocyte apoptosis, alteration of their chrono- and inotropic effects and electrophysiological characteristics. Their effects are transduced via 1-adrenergic receptors and depend on multiple factors as ligand properties, durability of its coupling with the receptor, amount of receptors on the cell surface, their affinity and conformation. Up to the present moment, reasons for autoimmune response and clinical significance of autoantibodies against 1-adrenergic receptors are not thoroughly understood. Autoantibodies against 1-adrenergic receptors can be removed from the bloodstream by immunoadsorption and thus development of validated methods of their identification is relevant.
Subject(s)
Arrhythmias, Cardiac/immunology , Autoantibodies , Cardiomyopathy, Dilated/immunology , Receptors, Adrenergic, beta-1/immunology , HumansABSTRACT
OBJECTIVE: This study aimed to assess the level of anti-1-adrenergic receptor autoantibodies in patients with ventricular arrhythmias with no signs of organic heart disease and with presence of cardiovascular pathology in comparison with a group of healthy volunteers. MATERIAL AND METHODS: The study included 44 patients with ventricular arrhythmias with no signs of organic heart disease ("idiopathic"), 34 patients with diagnosed dilated cardiomyopathy (DCM) of inflammatory origin, 35 patients with coronary heart disease and ventricular arrhythmias, 12patients with coronary heart disease with no ventricular arrhythmias, and 19 healthy volunteers (control group). The level of autoantibodies against the 1-adrenergic receptor was determined by the developed competitive cell-based enzyme-linked immunosorbent assay (ELISA) and by the standard ELISA using peptides corresponding to the second extracellular loop of the 1-adrenergic receptor. RESULTS: Elevated level of autoantibodies detected by a competitive cell-based ELISA was observed in 62% of patients with DCM compared to 21% of healthy volunteers (p=0.0006). In patients with "idiopathic" ventricular arrhythmias, the level of 1-adrenergic receptor autoantibodies was lower than in healthy subjects (p=0.003). Coronary heart disease patients with or without ventricular arrhythmias exhibited no differences from the control group. The number of significantly positive signals in peptide-based ELISA did not exceed 10% in any of the groups. No correlation between the data from competitive cell-based ELISA and peptide-based ELISA was found. CONCLUSIONS: This study demonstrated that competitive cell-based ELISA technique can be applied for detection of 1-adrenergic receptor autoantibodies. The results in DCM patients generally correspond to the expected. Decreased level of autoantibodies in patients with "idiopathic" ventricular arrhythmias indicates that this disease is related to changes in the immune system. Such relation is not observed in the case of coronary heart disease patients.
Subject(s)
Arrhythmias, Cardiac/immunology , Autoantibodies/blood , Receptors, Adrenergic, beta-1/immunology , Adult , Arrhythmias, Cardiac/blood , Arrhythmias, Cardiac/complications , Autoantibodies/immunology , Cardiomyopathy, Dilated/complications , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle AgedABSTRACT
We proposed a new method of evaluation of beta-receptor's activity on the surface of human T-lymphocytes based on the radioligand method. Optimal conditions for evaluation of specific binding to ß2-adrenoceptors of 0.5 fmol ligand per 1 million cells using [125I]-cyanopindolol were found. The possibility of using of ß2-adrenoceptor's activity assessment in clinical settings was demonstrated on human T-lymphocyte.
