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Activation of beta2-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I, and C-protein in ventricular myocardium from patients with terminal heart failure


, : Activation of beta2-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I, and C-protein in ventricular myocardium from patients with terminal heart failure. Circulation 99(1): 65-72

Background - Catecholamines hasten cardiac relaxation through beta-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of beta1- and beta2-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results - Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n = 5) or ischemic cardiomyopathy (n = 5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 mumol/L) or zinterol (10 mumol/L), mediated through beta2-adrenergic receptors, and of norepinephrine (10 mumol/L), mediated through beta1-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinephrine, zinterol, and norepinephrine increased contractile force to approximately the same extent, hastened the onset of relaxation by 15+-3%, 5+-2%, and 20+-3%, respectively, and reduced the time to half-relaxation by 26+-3%, 21+-3%, and 37+-3%. These effects of epinephrine, zinterol, and norepinephrine were associated with phosphorylation (pmol phosphate/mg protein) of phospholamban 14+-3, 12+-4, and 12+-3; troponin 140+-7, 33+-7, and 31+-6; and C-protein 7.2+-1.9, 9.3+-1.4, and 7.5+-2.0. Phosphorylation of phospholamban occurred at both Ser16 and Thr17 residues through both beta1- and beta2-adrenergic receptors. Conclusions - Norepinephrine and epinephrine hasten human ventricular relaxation and promote phosphorylation of implicated proteins through both beta1 and beta2-adrenergic receptors, thereby potentially improving diastolic function.

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PMID: 9884381


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