Autoantibodies against G-protein-coupled receptors modulate heart mast cells.

Mast cells are believed to be involved in myocardial tissue remodelling under pathophysiological conditions. We examined the effects of autoantibodies against G-protein-coupled receptors in sera of patients with heart diseases on myocardial mast cells in the cultured neonatal Sprague-Dawley rat heart cells. Cells collected at day 3 and 10 of the culture were preincubated with autoantibodies against alpha1-adrenoceptor and angiotensin II AT1-receptor, agonist phenylephrine and angiotensin II, and control IgG.

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.