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Keywords {🔍}

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Topics {✒️}

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Questions {❓}

• Dranse HJ, Kelly MEM, Hudson BD (2013) Drugs or diet?

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         headline:Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor
         description:Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.
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            Olfactory receptor
            Calcium transients
            Negative chronotropic effect
            Negative inotropic effect
            Medium-chain fatty acids
            Cardiology
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      headline:Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor
      description:Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.
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      dateModified:2017-01-23T00:00:00Z
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         Olfactory receptor
         Calcium transients
         Negative chronotropic effect
         Negative inotropic effect
         Medium-chain fatty acids
         Cardiology
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      name:E. Schleicher
      affiliation:
            name:University of Tuebingen
            address:
               name:Division of Pathobiochemistry and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany
               type:PostalAddress
            type:Organization
      name:L. Gelis
      affiliation:
            name:Ruhr-University Bochum
            address:
               name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
               type:PostalAddress
            type:Organization
      name:H. Hatt
      affiliation:
            name:Ruhr-University Bochum
            address:
               name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
      name:Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany
      name:DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
      name:Institute for Neurophysiology, University of Cologne, Cologne, Germany
      name:Division of Pathobiochemistry and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany
      name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
      name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
      name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
      name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
      name:Institute for Neurophysiology, University of Cologne, Cologne, Germany
      name:Institute for Neurophysiology, University of Cologne, Cologne, Germany
      name:Institute for Neurophysiology, University of Cologne, Cologne, Germany
      name:Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Ruhr-University Bochum, Bad Oeynhausen, Germany
      name:Division of Pathobiochemistry and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany
      name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany
      name:Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany

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