Both β 2 - and β 1 -Adrenergic Receptors Mediate Hastened Relaxation and Phosphorylation of Phospholamban and Troponin I in Ventricular Myocardium of Fallot Infants, Consistent With Selective Coupling of β 2 -Adrenergic Receptors to G s -Protein

Author:

Molenaar Peter1,Bartel Sabine1,Cochrane Andrew1,Vetter Donathe1,Jalali Homayoun1,Pohlner Peter1,Burrell Kylie1,Karczewski Peter1,Krause Ernst-Georg1,Kaumann Alberto1

Affiliation:

1. From the Departments of Medicine, The Prince Charles Hospital; Physiology and Pharmacology, University of Queensland, Queensland (P.M.); the Department of Pharmacology, University of Melbourne, Victoria, Australia (P.M., K.B.); Max-Delbrück Center of Molecular Medicine, Cardiology, Berlin, Germany (S.B., D.V., P.K., E.G.K.); Victorian Paediatric Cardiac Surgical Unit, Royal Children’s Hospital, Parkville, Australia (A.C.); the Department of Cardiac Surgery, The Prince Charles Hospital, Queensland ...

Abstract

Background —In adult human heart, both β 1 - and β 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 β 1 - and β 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 21/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of β 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 (−)-[ 125 I]-cyanopindolol, revealed a greater percentage of β 1 - (71%) than β 2 -adrenergic receptors (29%). Binding of (−)-epinephrine to β 2 -receptors underwent greater GTP shifts than binding of (−)-norepinephrine to β 1 -receptors. Conclusions —Despite their low density, β 2 -adrenergic receptors are nearly as effective as β 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

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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