Functional and structural characterization of anti-beta1-adrenoceptor autoantibodies of spontaneously hypertensive rats.
Eighteen month old spontaneously hypertensive rats (SHR-rats) showed myocardial dysfunction and autoantibodies directed against the beta1-adrenoceptor similarly as known in human dilated cardiomyopathy or Chagas' disease. The agonist-like antibodies were able to activate the beta1-adrenoceptor mediated signal transduction cascade in cultured rat cardiomyocytes and induced a long-lasting stimulatory effect resulting in a harmful adrenergic overdrive. The antibodies recognized an epitope of the second extracellular loop of the beta1-adrenoceptor identical to that epitope identified in Chagas' disease. In conclusion, our assumption is supported that old SHR-rat are an useful animal model for investigating the role of anti-beta1-adrenoceptor antibodies in the induction of human cardiomyopathy.
Max Delbrück Centrum für Molekulare Medizin, Berlin, Germany. gwalluk@mdc.berlin.de
Gerd
G
Wallukat
Svenia
S
Podlowski
Eberhard
E
Nissen
Rosemarie
R
Morwinski
Csaba
C
Csonka
Arpad
A
Tosaki
Ingolf E
IE
Blasig
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology*; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000276:immunology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D000939:Epitopes; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007136:Immunoglobulins / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology; D017725:Ventricular Pressure
D000319:Adrenergic beta-Antagonists; D001323:Autoantibodies; D000939:Epitopes; D007136:Immunoglobulins; D010455:Peptides; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C026777:ICI 118551; D000242:Cyclic AMP