Agonistic effects of anti-peptide antibodies and autoantibodies directed against adrenergic and cholinergic receptors: absence of desensitization.

Affinity-purified autoantibodies and anti-peptide antibodies directed against the second extracellular loop of the beta 1-adrenoceptor increase the beating rate of cultured cardiomyocytes just like the beta-adrenergic agonist isoprenaline. Their positive chronotropic action is blocked by beta-adrenergic antagonists. Affinity-purified autoantibodies and anti-peptide antibodies directed against the muscarinic cholinergic M2 receptor exert in these myocytes, like the muscarinic cholinergic agent carbachol, a negative chronotropic effect that is antagonized by atropine.

The beta 1-adrenoceptor as antigen: functional aspects.

The sera of patients with myocarditis and idiopathic dilated cardiomyopathy contain agonistic autoantibodies that bind to the beta 1-adrenoceptor. These antibodies recognize epitopes on either the first or second extracellular loop of this receptor and exert in cultured neonatal rat heart myocytes a positive chronotropic effect. This effect is eliminated by beta 1-adrenoceptor blockade as well as by peptides corresponding to the first or second extracellular loop of the human beta 1-adrenoceptor.

Anti-beta 1-adrenoceptor autoantibodies with chronotropic activity from the serum of patients with dilated cardiomyopathy: mapping of epitopes in the first and second extracellular loops.

In a preceding communication (Wallukat et al., 1992, Z Kardiol 81 [Suppl. 4]: 79-83), it was reported that synthetic peptides, corresponding in amino acid sequence to either the first or the second extracellular loop of the human beta 1-adrenoceptor, selectively suppressed the metoprolol- and bisoprolol-sensitive positive chronotropic action exerted in cultures of beating neonatal rat cardiomyocytes by the serum immunoglobulin fraction of patients with myocarditis and idiopathic dilated cardiomyopathy (DCM) and by affinity-purified autoantibodies from that fraction.

Supersensitivity to beta-adrenoceptor stimulation evoked in cultured neonatal rat heart myocytes by L(+)-lactate and pyruvate.

1. Cells from the ventricles of newborn rats were cultured for 8 days in flasks attached to a rocker apparatus to ensure an adequate oxygen supply. 2.

[Autoantibodies against the beta 1-adrenergic receptor in myocarditis and dilated cardiomyopathy: localization of two epitopes].

Sera of patients with myocarditis and dilated cardiomyopathy contain stimulatory autoantibodies directed specifically against the beta 1-adrenergic receptor. The binding of the antibodies could be localized to either the first or the second extracellular loop of the beta 1-adrenoceptor. In 73% of the cases investigated the antibodies recognized the second extracellular loop.