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Both beta2- and beta1-adrenergic receptors mediate hastened relaxation and phosphorylation of phospholamban and troponin I in ventricular myocardium of fallot infants, consistent with selective coupling ofbeta2-adrenergic receptors to G(s)-protein

Official URL:http://circ.ahajournals.org/cgi/content/abstract/102/15/1814
PubMed:View item in PubMed
Creators Name:Molenaar, P. and Bartel, S. and Cochrane, A. and Vetter, D. and Jalali, H. and Pohlner, P. and Burrell, K. and Karczewski, P. and Krause, E.G. and Kaumann, A.
Journal Title:Circulation
Journal Abbreviation:Circulation
Page Range:1814-1821
Date:10 October 2000
Keywords:Beta Adrenergic Receptors, Catecholamines, Myocardial Contraction, Tetralogy of Fallot
Abstract:Background - In adult human heart, both {beta} 1- and {beta} 2-adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of {beta} 1- and {beta} 2-adrenergic receptors on relaxation and phosphorylation of phospholamban and troponin I in ventricle obtained from infants with tetralogy of Fallot. Methods and Results - Myocardium dissected from the right ventricular outflow tract of 27 infants (age range 2 1/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of {beta} 1-adrenergic receptors with (-)-norepinephrine (NE) and β 2-adrenergic receptors with (-)-epinephrine (EPI) evoked phosphorylation of phospholamban (at serine-16 and threonine-17) and troponin I and caused concentration-dependent increases in contractile force (-log EC 50 [mol/L] NE 5.5±0.1, n= 12; EPI 5.6±0.1, n= 13 patients), hastening of the time to reach peak force (-log EC 50 [mol/L] NE 5.8±0.2; EPI 5.8±0.2) and 50% relaxation (-log EC 50 [mol/L] NE 5.7±0.2; EPI 5.8±0.1). Ventricular membranes from Fallot infants, labeled with (-)-[ 125I]-cyanopindolol, revealed a greater percentage of {beta} 1- (71%) than {beta} 2-adrenergic receptors (29%). Binding of (-)-epinephrine to {beta} 2-receptors underwent greater GTP shifts than binding of (-)-norepinephrine to {beta} 1-receptors. Conclusions - Despite their low density, {beta} 2-adrenergic receptors are nearly as effective as {beta} 1-adrenergic receptors of infant Fallot ventricle in enhancing contraction, relaxation, and phosphorylation of phospholamban and troponin I, consistent with selective coupling to G(s)-protein.
Publisher:American Heart Association (U.S.A.)
Item Type:Article

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