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Zur Funktion des β3-Adrenozeptors am Herzen: Signaltransduktion, inotroper Effekt und therapeutischer Ausblick

On the function of β3-adrenoceptors in the human heart: signal transduction, inotropic effect and therapeutic prospects

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Summary

β-adrenergic stimulation is an important regulatory mechanism of cardiac function. Next to β1- and β2-adrenoceptors, the expression of a third β-adrenoceptor population, the β3-adrenoceptor, has recently been evidenced in the human heart. Stimulation of cardiac β3-adrenoceptors leads to a decrease in contractility via a release of nitric oxide (NO). In this context, different molecular mechanisms of endothelial nitric oxide synthase (eNOS) activation have been uncovered to occur as a consequence of β3-adrenergic stimulation. In both nonfailing and failing myocardium, β3-adrenergic stimulation may have a protective effect against excessive chatecolaminergic stimulation as it occurs during somatic and mental stress and during heart failure. For this reason, the β3-adrenoceptor is discussed as a possible target for the pharmacological therapy of heart failure.

Zusammenfassung

Die β-adrenerge Stimulation ist einer der wichtigsten Regulationsmechanismen kardialer Funktion. Neben β1- und β2-Adrenorezeptoren wurde eine dritte β-Adrenozeptorpopulation im menschlichen Herzen nachgewiesen, der β3-Adrenozeptor. Die Stimulation kardialer β3-Adrenozeptoren führt über eine Ausschüttung von Stickoxid (NO) zu einer Herabsetzung der kardialen Kontraktilität. Dabei wurden verschiedene molekulare Mechanismen β3-adrenerger Aktivierung der endothelialen Stickoxidsynthase (eNOS) in Kardiomyozyten identifiziert. Im gesunden aber auch im insuffizienten Herzen könnte die β3-adrenerge Stimulation einen Schutzmechanismus gegen exzessive catecholaminerge Stimulation, wie sie bei körperlichem und psychischem Stress, sowie bei der Herzinsuffizienz auftritt, darstellen. Aus diesem Grund wird der β3-Adrenozeptor als Zielprotein für die Pharmakotherapie der Herzinsuffizienz diskutiert.

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Abbreviations

cAMP:

zyklisches Adenosinmonophosphat

cGMP:

zyklisches Guanosinmonophosphat

eNOS:

endotheliale Stickoxidsynthase

GI-protein:

inhibitorisches G-Protein

Gs-protein:

stimulierendes G-protein

L-NMA:

N-Nitro-L-Arginin

L-NAME:

N-Nitro-L-Argininmethylesterhydrochlorid

NO:

Stickoxid

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Authors and Affiliations

  1. Universitätsklinikum Münster, Medizinische Klinik und Poliklinik C für Kardiologie und Angiologie, Münster, Germany

    Christian Pott

  2. Labor für Herzmuskelphysiologie und Molekulare Kardiologie, Klinik III für Innere Medizin, Universität zu Köln, Köln, Germany

    Andreas Napp & Robert H.G. Schwinger

  3. Abteilung für Molekulare und Zelluläre Sportmedizin, Deutsche Sporthochschule Köln, Köln, Germany

    Dirk Steinritz, Wilhelm Bloch & Klara Brixius

  4. Institut für Pharmakologie und Toxikologie der Bundeswehr, München, Germany

    Dirk Steinritz

  5. Medizinische Klinik II, Klinikum Weiden, Weiden i.d. Oberpfalz, Germany

    Robert H.G. Schwinger

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  1. Christian Pott
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  2. Dirk Steinritz
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Pott, C., Steinritz, D., Napp, A. et al. Zur Funktion des β3-Adrenozeptors am Herzen: Signaltransduktion, inotroper Effekt und therapeutischer Ausblick. Wien Med Wochenschr 156, 451–458 (2006). https://doi.org/10.1007/s10354-006-0273-x

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