beta(1)-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 Ca(2+) transient and cell shortening of rat cardiomyocytes measured by confocal-laser-scanning-microscopy. beta(1)-adrenoceptor antibodies caused a dose-related increase in Ca(2+) 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.
Staudt
A
A
Klinik für Innere Medizin B, Medizinische Fakultät, Ernst-Moritz-Arndt-Universität, Fr.-Loefflerstr. 23a, D-17487 Greifswald, Germany. staudt@mail.uni-greifswald.de
Mobini
R
R
Fu
M
M
Grosse
Y
Y
Stangl
V
V
Stangl
K
K
Thiele
A
A
Baumann
G
G
Felix
S B
SB
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry / Q000276:immunology*; D013873:Thionucleotides / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000911:Antibodies, Monoclonal; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C026777:ICI 118551; D000242:Cyclic AMP; D008790:Metoprolol; D007545:Isoproterenol