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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Transgenic Studies of Cardiac Adrenergic Receptor Regulation

Andrea D. Eckhart and Walter J. Koch
Journal of Pharmacology and Experimental Therapeutics October 2001, 299 (1) 1-5;
Andrea D. Eckhart
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Walter J. Koch
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Abstract

An accumulation of recent data on genetically engineered mouse models suggests that results from studies done in vitro are not necessarily duplicated in vivo. The genetic manipulation of the adrenergic receptor (AR) signaling system in the heart has afforded us the opportunity to not only study the physiological impact of AR signaling manipulation but also to examine how the various components interact with one another in vivo. In particular, although members of the G protein-coupled receptor kinase family do not exhibit substrate selectivity when overexpressed in cell culture, in vivo selectivity is apparent when examined in the cardiovascular system of genetically engineered mice. Additionally, transgenic expression of peptide inhibitors of signaling represents a powerful tool to examine specific targets in order to determine their contribution to a physiologic phenotype following stimulation. Finally, in vivo manipulation of the AR system has provided a broader understanding of the role that various G protein-coupled receptors play in situations where multiple members contribute to a phenotype. Thus, although in vitro studies allow for a more defined environment in which to study the signaling mediated by various receptors, it is essential to verify these findings in vivo to confirm or refute in vitro results.

Footnotes

  • Abbreviations:
    GPCR
    G protein-coupled receptor
    GRK
    GPCR kinases
    AR
    adrenergic receptor
    PLC
    phospholipase C
    DAG
    diacylglycerol
    MAP kinase
    mitogen-activated protein kinase
    GqI
    inhibitor of Gq
    βARK
    β-adrenergic receptor kinase
    βARKct
    carboxyl-terminal portion of βARK
    HEK
    human embryonic kidney
    αMHC
    α-myosin heavy chain
    PLB
    phospholamban
    TAC
    transverse aortic constriction
    • Received February 28, 2001.
    • Accepted May 10, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 299 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 1
1 Oct 2001
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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Transgenic Studies of Cardiac Adrenergic Receptor Regulation

Andrea D. Eckhart and Walter J. Koch
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 1-5;

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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Transgenic Studies of Cardiac Adrenergic Receptor Regulation

Andrea D. Eckhart and Walter J. Koch
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 1-5;
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  • Article
    • Abstract
    • Use of Transgenic Models to Delineate in Vivo GRK Selectivity
    • Use of Transgenic Mice to Delineate Differences in Cardiac βAR Signaling
    • Gene Knockout Strategies in the Mouse to Study βAR Function
    • Inhibition of GRK2 in the Heart Has Therapeutic Potential
    • Consequences of Specific Inhibition of Myocardial Gq-Mediated Signaling
    • Conclusions and Future Directions
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