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(Circulation. 2000;102:1814.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Both ß₂- and ß₁-Adrenergic Receptors Mediate Hastened Relaxation and Phosphorylation of Phospholamban and Troponin I in Ventricular Myocardium of Fallot Infants, Consistent With Selective Coupling of ß₂-Adrenergic Receptors to G_s-Protein

Peter Molenaar, PhD; Sabine Bartel, PhD; Andrew Cochrane, MBBS, FRACS; Donathe Vetter, TA; Homayoun Jalali, MD; Peter Pohlner, MBBS, FRACS; Kylie Burrell, BScHons; Peter Karczewski, PhD; Ernst-Georg Krause, PhD; Alberto Kaumann, MD, PhD

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 (H.J., P.P.); Babraham Institute, Cambridge, and the Department of Physiology, University of Cambridge, UK (A.K.).

Correspondence to Dr Peter Molenaar, Department of Medicine, University of Queensland, The Prince Charles Hospital, Chermside, Queensland, 4032, Australia. E-mail molenaar{at}medicine.uq.edu.au

Background—In adult human heart, both ß₁- and ß₂-adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of ß₁- and ß₂-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 ß₁-adrenergic receptors with (-)-norepinephrine (NE) and ß₂-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 EC₅₀ [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 EC₅₀ [mol/L] NE 5.8±0.2; EPI 5.8±0.2) and 50% relaxation (-log EC₅₀ [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 ß₁- (71%) than ß₂-adrenergic receptors (29%). Binding of (-)-epinephrine to ß₂-receptors underwent greater GTP shifts than binding of (-)-norepinephrine to ß₁-receptors.

Conclusions—Despite their low density, ß₂-adrenergic receptors are nearly as effective as ß₁-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.

Key Words: tetralogy of Fallot • catecholamines • myocardial contraction • receptors, adrenergic, beta

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