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Uncoupling of the β2-Adrenoceptor Effect on Ca2+ Regulation and cAMP in Cardiac Cells

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Molecular and Cellular Mechanisms of Cardiovascular Regulation

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Summary

Studies in rat ventricular myocytes demonstrate that while both β1-adrenergic receptor stimulation (β1ARS) and β2AR stimulation (β2ARS) increase cyclic adenosine monophosphate (cAMP) to a similar extent, the effects of β2ARS on cytosolic Ca2+ (Cai) transient and contraction are largely dissociated from the cAMP increase. In canine ventricular myocytes, β2ARS augments the amplitude of ICa, Cai transient, and contraction without increasing cell cAMP. In rat cells, β2ARS by zinterol (ZINT) or by isoproterenol in the presence of the selective β1AR antagonist CGP 20712A increases contraction amplitude to about the same extent as β1ARS by norepinephrine (NE). While β1ARS has a potent effect to abbreviate the durations of the contraction and Cai transient, β2ARS has only a minor relaxation effect in rat cells. β2ARS does not result in phospholamban phosphorylation to the same extent in either rat or canine cells as does β1ARS. In addition, β1ARS, but not β2ARS, increases the diastolic Ca2+ level and evokes spontaneous Cai oscillations. β2ARS prolongs the action potential to a greater extent than does β1ARS. β1ARS and β2ARS also differ in their effects on ICa: whereas both increase the peak ICa amplitude to a similar extent, only β2ARS markedly prolongs the ICa inactivation time. A peptide inhibitor of protein kinase A abolishes β1ARS, but only partially affects β2ARS-induced increase in ICa in canine cells; the β2AR effect to increase ICa is abolished by a G protein inhibitor, GDPβS. Additionally, the Gs-coupled β2AR activates a pertussis toxin (PTX)-sensitive G protein pathway that leads to inhibition of its effects. This provides a mechanism to protect the heart from Ca2+ overload and arrhythmias during the response in stress.

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Authors and Affiliations

  1. Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA

    Rui-Ping Xiao & Edward G. Lakatta

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  1. Rui-Ping Xiao
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  2. Edward G. Lakatta
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Editor information

Editors and Affiliations

  1. Department of Pharmacology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, 990-23, Yamagata, Japan

    Masao Endoh M.D., Ph.D. (Professor) (Professor)

  2. Georgetown University Medical Center, 3900 Reservoir Rd., NW, 20007, Washington, D.C., USA

    Martin Morad Ph.D. (Professor of Pharmacology and Medicine) (Professor of Pharmacology and Medicine)

  3. Pharmakologisches Institut, Universitäts-Krankenhaus Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany

    Hasso Scholz M.D. (Professor) (Professor)

  4. Department of Pharmacology, Akita University School of Medicine, 1-1-1 Hondoh, Akita 010, Japan

    Toshihiko Iijima M.D., Ph.D. (Professor) (Professor)

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© 1996 Springer Japan

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Xiao, RP., Lakatta, E.G. (1996). Uncoupling of the β2-Adrenoceptor Effect on Ca2+ Regulation and cAMP in Cardiac Cells. In: Endoh, M., Morad, M., Scholz, H., Iijima, T. (eds) Molecular and Cellular Mechanisms of Cardiovascular Regulation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-65952-5_23

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  • DOI: https://doi.org/10.1007/978-4-431-65952-5_23

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-65954-9

  • Online ISBN: 978-4-431-65952-5

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