| Beta-adrenergic receptor-dependent and -independent stimulation of adenylate cyclase is impaired during severe sepsis in humans. | |
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MedLine Citation:
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PMID: 9885886 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: a) To investigate the functional consequences of sepsis on the beta-adrenergic signal transduction in human circulating lymphocytes; b) to appreciate sepsis-associated catecholamine and cytokine release. DESIGN: Experimental, comparative study. SETTING: Research laboratory in a university hospital. SUBJECTS: Healthy controls (n = 10); critically ill patients who were not septic (n = 7); septic patients with severe sepsis or septic shock (n = 11). MEASUREMENTS AND MAIN RESULTS: Experiments were carried out using freshly isolated peripheral blood mononuclear cells (PBMC). We measured beta-adrenergic receptor (betaAR) number and affinity, and intracellular cAMP content at baseline and after the pharmacological stimulation of each component of the beta-adrenergic complex: betaAR with isoproterenol, Gs-protein with sodium fluoride (NaF), adenylate cyclase with forskolin. Catecholamine (adrenaline, noradrenaline) and cytokine (TNFalpha, IL-1alpha, IL-1beta, IL-6) serum levels were measured. In both septic and non-septic patients we observed a similar 40 % down-regulation of betaARs compared to controls, and a reduced basal and isoproterenol-stimulated cAMP accumulation (p < 0.05). The cAMP production elicited by NaF or forskolin was lower in septic patients than in the controls (p < 0.01). Forskolin-stimulated cAMP accumulation was significantly lower in septic patients than it was in non-septic ones (p < 0.001). Catecholamine serum concentrations were increased in the two patient groups without any significant difference. Elevated cytokine serum levels were detected in 45% of the septic patients (versus 14% of non-septic patients p < 0.05). CONCLUSIONS: Patients presenting with severe sepsis or septic shock have extended postreceptor defects of the beta-adrenergic signal transduction. This finding suggests a heterologous desensitization of adenylate cyclase stimulation. |
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Authors:
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G Bernardin; A D Strosberg; A Bernard; M Mattei; S Marullo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Intensive care medicine Volume: 24 ISSN: 0342-4642 ISO Abbreviation: Intensive Care Med Publication Date: 1998 Dec |
Date Detail:
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Created Date: 1999-03-29 Completed Date: 1999-03-29 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7704851 Medline TA: Intensive Care Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1315-22 Citation Subset: IM |
Affiliation:
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Service de Réanimation Médicale, Hôpital de l'Archet, Nice, France. gbernard@unice.fr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Cyclase
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metabolism* Adult Aged Case-Control Studies Catecholamines / blood* Cyclic AMP / metabolism Cytokines / blood* Female Humans Lymphocytes / metabolism Male Middle Aged Receptors, Adrenergic, beta / metabolism* Shock, Septic / blood, metabolism* Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Catecholamines; 0/Cytokines; 0/Receptors, Adrenergic, beta; 60-92-4/Cyclic AMP; EC 4.6.1.1/Adenylate Cyclase |
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