Abstract
Heart failure is a problem of increasing importance in medicine. An important characteristic of heart failure is reduced agonist-stimulated adenylyl cyclase activity (receptor desensitization) due to both diminished receptor number (receptor down regulation) and impaired receptor function (receptor uncoupling). These changes in the ß-adrenergic receptor (ß-AR) system, may in part account for some of the abnormalities of contractile function in this disease. Myocardial contraction is closely regulated by Gprotein coupled ß-adrenergic receptors through the action of the second messenger cAMP. The ß-AR receptors themselves are regulated by a set of specific kinases, termed the Gprotein-coupled receptor kinases (GRKs). The study of this complex system in vivo has recently been advanced by the development of transgenic and gene targeted (“knockout”) mouse models. Combining transgenic technology with sophisticated physiological measurements of cardiac hemodynamics is an extremely powerful strategy to study the regulation of myocardial contractility in the normal and failing heart.
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Rockman, H.A. (1997). Uncoupling of G-Protein Coupled Receptors in vivo: Insights from Transgenic Mice. In: Sideman, S., Beyar, R. (eds) Analytical and Quantitative Cardiology. Advances in Experimental Medicine and Biology, vol 430. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5959-7_6
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DOI: https://doi.org/10.1007/978-1-4615-5959-7_6
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