Both beta(2)- and beta(1)-adrenergic receptors mediate hastened relaxation and phosphorylation of phospholamban and troponin I in ventricular myocardium of Fallot infants, consistent with selective coupling of beta(2)-adrenergic receptors to G(s)-protein.
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.


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 beta(1)-adrenergic receptors with (-)-norepinephrine (NE) and beta(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 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.
Molenaar
P
P
Department of Medicine, The Prince Charles Hospital, University of Queensland, Australia. molenaar@medicine.uq.edu.au
Bartel
S
S
Cochrane
A
A
Vetter
D
D
Jalali
H
H
Pohlner
P
P
Burrell
K
K
Karczewski
P
P
Krause
E G
EG
Kaumann
A
A
D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002675:Child, Preschool; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013771:Tetralogy of Fallot / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism*; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D004837:Epinephrine; D019205:GTP-Binding Protein alpha Subunits, Gs; D006160:Guanosine Triphosphate; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D012694:Serine; D013912:Threonine; D019210:Troponin I; D000099211:Phospholamban