β1-adrenoceptor antibodies induce positive inotropic response in isolated cardiomyocytes

beta (1)-adrenoceptor autoantibodies are present in approximately 30% of patients suffering from dilated cardiomyopathy. The inotropic effects mediated by these antibodies remain to be studied. Monoclonal antibodies were raised against a peptide corresponding to the second extracellular loop of the human beta (1)-adrenoceptor in balb/C mouse(n = 6), and were characterized by enzyme immunoassay after purification by protein A. Purified immunoglobulin G from non-immunized animals (controls) did not influence Ca2+ transient and cell shortening of rat cardiomyocytes measured by confocal-laser-scanning-microscopy. beta (1)-adrenoceptor antibodies caused a dose-related increase in Ca2+ transient (dilution 1:2: + 35.3 +/- 5.1%), and in cell shortening (dilution 1:2: + 40.5 +/- 6.3%) (P < 0.01 vs. controls). The effect of the <beta>(1)-adrenoceptor antibodies was blocked by the antigenic peptide and by the antagonist metoprolol. In addition, beta (1)-adrenoceptor antibodies induced a dose-dependent increase of the cyclic adenosine monophosphate. The inotropic response induced by isoproterenol was attenuated by the beta (1)-adrenoceptor antibody. beta (1)-adrenoceptor antibodies as partial agonists induce a specific positive inotropic effect via the protein-kinase-A-cascade. (C) 2001 Elsevier Science B.V. All rights reserved.