RT Journal Article
SR Electronic
T1 β-Adrenergic Receptor Subtype-Specific Signaling in Cardiac Myocytes from β<sub>1</sub> and β<sub>2</sub> Adrenoceptor Knockout Mice
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 577
OP 583
VO 60
IS 3
A1 Eric Devic
A1 Yang Xiang
A1 Dianna Gould
A1 Brian Kobilka
YR 2001
UL http://molpharm.aspetjournals.org/content/60/3/577.abstract
AB The sympathetic nervous system modulates cardiac contractility and rate by activating β-adrenergic receptors (βAR) expressed on cardiac myocytes and specialized cells in the sinoatrial node and the conduction system. Recent clinical studies have suggested that β-adrenergic receptors also play a role in cardiac remodeling that occurs in the pathogenesis of cardiomyopathy. Both β1 and β2 adrenergic receptors are expressed in human and murine hearts. We have examined the effect of βAR activation on the spontaneous contraction rate of neonatal myocyte cultures from wild-type and β receptor knockout (KO) mice (β1AR-KO, β2AR-KO and β1β2AR-KO mice). Stimulation of the β1AR in β2AR-KO myocytes produces the greatest increase in contraction rate through a signaling pathway that requires protein kinase A (PKA) activation. In contrast, stimulation of the β2AR in β1AR-KO myocytes results in a biphasic effect on contraction rate with an initial increase in rate that does not require PKA, followed by a decrease in rate that involves coupling to a pertussis toxin sensitive G protein. A small isoproterenol-induced decrease in contraction rate observed in β1β2AR-KO myocytes can be attributed to the β3AR. These studies show that all three βAR subtypes are expressed in neonatal cardiac myocytes, and the β1AR and β2AR couple to distinct signaling pathways. The American Society for Pharmacology and Experimental Therapeutics