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Vol. 299, Issue 1, 1-5, October 2001

Transgenic Studies of Cardiac Adrenergic Receptor Regulation

Andrea D. Eckhart and Walter J. Koch

Department of Surgery, Duke University Medical Center, Durham, North Carolina

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.

0022-3565/01/2991-0001$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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