Alterations in beta-adrenoceptor density on T-lymphocytes upon activation with interleukin-2 and phytohaemagglutinin.

Cultivation of human peripheral blood T-lymphocytes in the presence of interleukin-2 (IL-2) and phytohaemagglutinin (PHA) caused biphasic alterations in the beta 2-adrenoceptor density (Bmax) and cAMP content of these cells. The increase in Bmax after 18 h incubation with IL-2 and PHA was due to the expression of the receptors in a low-affinity state. The stimulatory effect of isoproterenol on adenylate cyclase activity and its effect on cAMP content remained unchanged, indicating uncoupling between the expressed receptors and regulatory Gs-proteins. The addition of phorbolmyristateacetate (PMA), a protein kinase C activator, also caused a biphasic change in beta 2-adrenoceptor density on the surface of the cells. The data point to the involvement of protein kinase C in the mechanism responsible for the increase and subsequent decrease in beta 2-adrenoceptor density seen after activation of T-lymphocytes.

Interleukin-2- and phytohemagglutinin-activated proliferation of human T-lymphocytes is accompanied by stimulation of phosphoinositide turnover.

Interleukin-2 (IL-2) was more effective than phytohemagglutinin (PHA) in increasing the proliferative activity of human T-lymphocytes. Unlike PHA, IL-2 stimulated phosphoinositide turnover (PI turnover) only in those T-lymphocytes which had been preactivated by PHA with IL-2 and expressed the IL-2 receptors. The effect of PHA on PI turnover was, in general, stronger than that of IL-2. These results indicate that IL-2 and PHA-activated proliferation of human T-lymphocytes is accompanied by stimulation of PI turnover. However, IL-2-induced proliferative response may not be a direct consequence of PI turnover stimulation in these cells.

[Dependence of kinetic constants of intact human lymphocyte beta2-adrenoreceptors on the nature of the radioligands used]. / Zavisimost' kineticheskikh konstant beta2-adrenoretseptorov intaktnykh limfotsitov cheloveka ot prirody primeniaemykh radioligandov.

An analysis of human peripheral blood intact mononuclear lymphocyte beta 2-adrenoreceptors showed that the hydrophilic radioligand 3H-CGP-12177 binds at various temperatures only to surface receptors. The density of receptors as determined by the binding of the lipophilic antagonist 125I-CYP at 37 degrees C is 2 times as high as that at 4 degrees C. The affinity of lymphocyte beta 2-adrenoceptors for 1-isoproterenol measured by the labeled ligand displacement at low (4 degrees C) temperatures is by two or three orders of magnitude higher than that at 37 degrees C. The thiol-alkylating agent, N-ethylmaleimide (NEM) causes oppositely directed changes in the density of beta 2-adrenoceptors on intact lymphocytes depending on their original density. NEM increases the affinity of beta 2-adrenoreceptors for the hormone (1.5-12-fold). The state and regulation of human peripheral blood lymphocyte beta 2-adrenoreceptors depend on the hormonal status of patients at the moment of blood sample collection.

[Effect of physical load and brief monotherapy with obsidan on the characteristics of beta 2-adrenoreceptors of intact lymphocytes in patients with hypertension]. / Vliianie fizicheskoi nagruzki i korotkogo kursa monoterapii obzidanom na kharakteristiki beta 2-adrenoretseptorov intaktnykh limfotsitov bol'nykh gipertonicheskoi bolezn'iu.

Lymphocytes beta 2-receptor density (LBRD) was studied by binding with 125ICYP in 18 male patients with mild/moderate essential hypertension (EH) before and after propranolol monotherapy. In 5 of these patients LBRD was determined before and after dynamic exercise also. Propranolol therapy evoked different changes in LBRD in patients with EH. According to these results, all the patients were divided into 2 groups: the patients who respond to propranolol administration by an increase in the LBRD were attributed to the 1 group. If the LBRD decreased after propranolol, the patients were attributed to the 2 group. Propranolol had pronounced hypotensive effect in the 2 group and no hypotensive effect in the 1 group. Heart rate was significantly higher initially and decreased significantly more after treatment in the 2 group. In this group initial values of LBRD were significantly higher than in the 1 group. Exercise produced different changes in LBRD, which correlated with the changes produced by propranolol treatment. The positive correlations were found between LBRD and left ventricular myocardial mass and interventricular septum thickness. The data obtained indicate that LBRD is regulated in a qualitatively different manner in the two groups of patients with EH which appears to be related to baseline renin or perhaps catecholamine levels.

[The density of lymphocyte beta 2-adrenoreceptors and blood plasma catecholamines in patients with dilated cardiomyopathy]. / Plotnost' beta 2-adrenoretseptorov limfotsitov i katekholaminy plazmy krovi u bol'nykh dilatatsionnoi kardiomiopatiei.

27 patients with dilated cardiomyopathy (DCM) complicated by heart failure (HF) of stages I-IIB were studied. The density of lymphocyte beta 2-adrenoceptors decreased significantly as HF progressed. The level of circulating catecholamines (epinephrine, norepinephrine) was significantly higher in patients were severe HF, which probably caused more evident decrease in lymphocyte beta 2-adrenoceptors density in these patients. This point of view was confirmed by the data of correlation-regression analysis between the general beta 2-adrenoceptors density and hemodynamics data. The identified changes in the number of adrenoceptors reflect the process of cellular receptors desensitization. They should be considered as a possible mechanism of HF development on a molecular level that cause development of refractoriness to routine therapy.

Characteristics of lymphocyte beta-adrenoceptors in essential hypertension: effects of propranolol treatment and dynamic exercise.

The density of beta 2-receptors in intact lymphocytes was studied by binding with 125iodo-cyanopindolol in 18 male patients with mild or moderate hypertension before and after monotherapy with propranolol. The density of these receptors was also determined in 5 patients before and after dynamic exercise. We found that propranolol therapy evoked different changes in the density of beta-receptors in patients with essential hypertension. Based on these results, all patients were divided into two groups: (a) patients who responded to the administration of propranolol by an increase in receptor density and (b) patients who responded with a decrease in receptor density. Propranolol therapy had a pronounced hypotensive effect in the second group and no hypotensive effect in the first group. In the second group, heart rate was significantly higher initially and showed a significantly greater decrease after treatment. The initial values for beta 2-receptor density were also significantly higher in this group than in the first group. Mean values of baseline plasma renin activity (PRA) were higher in the second group, but this difference was nonsignificant. The 5 patients who participated in dynamic exercise exhibited different changes in beta-receptor density, which correlated with the changes observed with propranolol treatment. There was no correlation between PRA and the density of beta 2-receptors in lymphocytes. Positive correlations were found between the density of these receptors and left-ventricular myocardial mass and interventricular septal thickness. The data indicate that the density of these receptors in lymphocytes is regulated in a qualitatively different manner in the two groups of patients with essential hypertension; this difference appears to be related to baseline renin levels or, perhaps, catecholamine levels. Additional studies are needed to clarify the regulation of beta 2-receptors in essential hypertension.

[Effect of a physical load on the adrenergic receptor function of peripheral blood lymphocytes and thrombocytes in healthy donors]. / Vliianie fizicheskoi nagruzki na sostoianie adrenergicheskikh retseptorov limfotsitov i trombotsitov perifericheskoi krovi zdorovykh donorov.

Beta 2-adrenergic receptor density and platelet adenylate cyclase activity were determined in the peripheral blood of healthy donors during short-term physical exercise and compared to changes in biochemical parameters. The data obtained indicate the activation of sympathetic-adrenal system in general and suggest phasic regulation of catecholamine beta-adrenergic receptors.