Prolonged Isoproterenol Treatment Alters Immunoregulatory Cell Traffic and Function in the Rat

Murray, David R.; Polizzi, Susan; Harris, Tamara J.; Wilson, Nevin W.; Michel, Martin C.; Maisel, Alan

doi:10.1006/brbi.1993.1005

Cited by 17 publications

(5 citation statements)

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“…Elevations of lymphocyte cyclic AMP inhibit lymphocyte activation, proliferation and effector functions in vitro (Bourne et al, 1974;Kammer, 1988). In vivo cyclic AMP elevating agents such as the P-adrenoceptor agonists cause lymphopaenia in man (Maisel et al, 1990a) and reduce splenic weight in rats (Murray et al, 1993), whereas P-adrenoceptor agonists can increase the number of circulating T-cells in man (Maisel et al, 1991). Whether enhanced lymphocyte cyclic AMP formation is at least partly relevant for the immunosuppressive effects of glucocorticoids in vivo cannot be answered from the present in vitro data.…”

Section: Discussionmentioning

confidence: 99%

Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for increased function of the adenylyl cyclase catalyst

Michel

Knapp

Ratjen

1994

British J Pharmacology

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1 Glucocorticoids and elevations of intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) may affect lymphocyte activation, proliferation and effector functions in similar ways. Therefore, we have investigated the effects of the glucorticoid, dexamethasone, on human lymphocyte cyclic AMP formation.2 Treatment of resting human lymphocytes with the glucocorticoid, dexamethasone, sensitized prostaglandin E2-stimulated cyclic AMP accumulation in a time-and concentration-dependent manner. 3 In membranes of lymphocytes treated for 24h with 100nM dexamethasone, maximal adenylyl cyclase activity stimulated by prostaglandin E2, isoprenaline, guanosine 5'-triphosphate (GTP), forskolin and MnCl2 was significantly enhanced; the ECQ0 for these agents was not significantly altered.4 132-Adrenoceptor density, immunodetectable a-subunits of the G-proteins G, and Gi, and pertussis toxin-substrates were not significantly altered by dexamethasone treatment. 5 In dexamethasone-treated lymphocytes, prostaglandin E2-mediated inhibition of concanavalin Ainduced Ca2' elevations was doubled compared to control cells.6 Based on these data and the observation that enhancement of forskolin-and MnCl2-stimulated adenylyl cyclase activity could quantitatively account for the enhancement of prostaglandin E2-, isoprenaline-or GTP-stimulated adenylyl cyclase activity, we conclude that dexamethasone treatment sensitizes cyclic AMP formation in resting human lymphocytes by altering the adenylyl cyclase catalyst rather than G-proteins or hormone receptors. This results in an enhanced capability of cyclic AMP generating agonists to inhibit early steps of lymphocyte activation.

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Section: Discussionmentioning

confidence: 99%

Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for increased function of the adenylyl cyclase catalyst

Michel

Knapp

Ratjen

1994

British J Pharmacology

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“…Endogenous (splenic) catecholamines released due to stress or exogenous catecholamines can decrease splenic lymphocyte counts by redistribution of these cells to blood. (Ernstrom and Sandberg 1973;Ernstrom and Soder 1975;Iversen et al 1994;Murray et al 1993;Stevenson et al 2001). In general, the contribution of this effect to altered lymphocyte counts during stress is modest relative to the parts played by lymphocyte depots in the thymus and lymph nodes.…”

Section: Catecholaminesmentioning

confidence: 99%

Interpreting Stress Responses during Routine Toxicity Studies

et al. 2013

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Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic-pituitary-adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article-related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias.This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters evaluated in toxicity studies:

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“…The abundance of the subsets of cells from the immune system changes considerably in immunologic responses, inflammation, and stress (see, e.g., Ref. 31), and this reorganization also involves changes in the expression of ␤-ARs on cells (21,27) as well as the apoptotic regulation of cell survival (e.g., Ref. 43), which can be modulated by activation of the cAMP-dependent signaling pathway (see, e.g., Refs.…”

Section: G651 Clenbuterol Prevents Liver Apoptosis In Vivomentioning

confidence: 99%

β₂-Adrenergic receptor-selective agonist clenbuterol prevents Fas-induced liver apoptosis and death in mice

André

Gaston

Erraji

et al. 1999

American Journal of Physiology-Gastrointestinal and Liver Physi

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Stimulation of the cAMP-signaling pathway modulates apoptosis in several cell types and inhibits Jo2-mediated apoptosis in cultured rat hepatocytes. No information is yet available as to whether the hepatic β2-adrenergic receptor (AR) expression level, including β2-AR-dependent adenylyl cyclase activation, modulates hepatocyte sensitivity to apoptosis in vivo or whether this sensitivity can be modified by β2-AR ligands. We have examined this using C57BL/6 mice, in which hepatic β2-AR densities are low, and transgenic F28 mice, which overexpress β2-ARs and have elevated basal liver adenylyl cyclase activity. The F28 mice were resistant to Jo2-induced liver apoptosis and death. The β-AR antagonist propranolol sensitized the F28 livers to Jo2. In normal mice clenbuterol, a β2-AR-specific agonist, considerably reduced Jo2-induced liver apoptosis and death; salbutamol, another β2-AR-selective agonist, also reduced Jo2-induced apoptosis and retarded death but with less efficacy than clenbuterol; and propranolol blocked the protective effect of clenbuterol. This indicates that the expression level of functional β2-ARs modulates Fas-regulated liver apoptosis and that this apoptosis can be inhibited in vivo by giving β2-AR agonists. This may well form the basis for a new therapeutic approach to diseases involving abnormal apoptosis.

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Prolonged Isoproterenol Treatment Alters Immunoregulatory Cell Traffic and Function in the Rat

Cited by 17 publications

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Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for increased function of the adenylyl cyclase catalyst

Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for increased function of the adenylyl cyclase catalyst

Interpreting Stress Responses during Routine Toxicity Studies

β₂-Adrenergic receptor-selective agonist clenbuterol prevents Fas-induced liver apoptosis and death in mice

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Prolonged Isoproterenol Treatment Alters Immunoregulatory Cell Traffic and Function in the Rat

Cited by 17 publications

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Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for increased function of the adenylyl cyclase catalyst

Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for increased function of the adenylyl cyclase catalyst

Interpreting Stress Responses during Routine Toxicity Studies

β2-Adrenergic receptor-selective agonist clenbuterol prevents Fas-induced liver apoptosis and death in mice

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β₂-Adrenergic receptor-selective agonist clenbuterol prevents Fas-induced liver apoptosis and death in mice