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Autoantibodies against cardiac β1-adrenoceptor do not affect the low-affinity state β1-adrenoceptor-mediated inotropy in rat cardiomyocytes

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Circulating autoantibodies directed against the 2nd extracellular loop (EL-2) of β1-adrenoceptors (β1-AABs) have been detected in the serum of patients with various cardiovascular pathologies. β1-AABs induce agonistic, positive inotropic effects via β1-adrenoceptors (β1ARs). In the mammalian heart, β1-AR can exist in 2 distinct activated configurations (the so-called high- and low-affinity states). The aim of the present study was to investigate whether the action of β1-AAB is dependent on the affinity state of β1AR in isolated ventricular cardiomyocytes of adult Wistar rats. Immunoglobulin G (IgG) containing β1-AAB obtained from animals immunized with a peptide corresponding to the EL-2 of human β1-AR, caused a dose-dependent increase in cell shortening. Isoproterenol-induced inotropy was significantly reduced in cardiomyocytes that had been preincubated with IgG containing β1-AAB and in cardiomyocytes isolated from immunized rats. The negative effects of preincubation with IgG containing β1-AAB on the response to isoproterenol was inhibited in the presence of bisoprolol. CGP 12177A and pindolol-induced inotropy was not affected by IgG preincubation or immunization. No detectable inotropic effect of cell shortening was obtained with IgG containing β1-AAB in the presence of propranolol and 3-isobutyl-1-methylxanthine. The present study demonstrates that β1-AABs have no agonist/antagonist-like effects upon low-affinity state β1-ARs. This result indicates that β1-AABs recognize and stabilize the high-affinity state, but are unable to stabilize and (or) induce the low-affinity state receptor.
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Keywords: adrénorécepteur β1; autoantibody; autoanticorps; cardiomyocyte; cell shortening; high-affinity state; low-affinity state; raccourcissement cellulaire; rat; site de faible affinité; site de haute affinité; β1-adrenoceptor

Document Type: Research Article

Affiliations: 1: L’Université Nantes Angers Le Mans (LUNAM) – Oniris, UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle, Atlanpole-La Chantrerie, BP 40706, Nantes, F-44307, France. 2: L’Université Nantes Angers Le Mans (LUNAM) – Oniris, Biotechnologie Pathologie Reproduction/RSB, Atlanpole-La Chantrerie, BP 40706, Nantes, F-44307, France.

Publication date: April 1, 2012

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