[Interaction of chagasic autoantibodies with the third extracellular domain of the human heart muscarinic receptor. Functional and pathological implications].
Herein we demonstrate by ELISA and immunoblotting the presence in the sera of chagasic patients of circulating autoantibodies against the third extracellular domain of human muscarinic acetylcholine receptors by using a synthetic peptide corresponding to the sequence 169-192 of the receptor. Immunoaffinity purified antipeptide antibodies displayed cardiac muscarinic activity as decreased contractility and cAMP production and increased cGMP levels. These effects were specifically blocked by the synthetic peptide and by atropine. A strong association between the existence of circulating autoantibodies and the presence of dysautonomia was shown, making these autoantibodies an appropriate marker of heart autonomic dysfunction.
Goin
J C
JC
Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Facultade de Odontología, Universidad de Buenos Aires, Argentina.
Pérez Leirós
C
C
Borda
E
E
Sterin-Borda
L
L
D000328:Adult; D001323:Autoantibodies / Q000302:isolation & purification*; D001342:Autonomic Nervous System Diseases / Q000276:immunology; D015415:Biomarkers; D014355:Chagas Disease / Q000097:blood / Q000276:immunology*; D000242:Cyclic AMP; D006152:Cyclic GMP; D006801:Humans; D008875:Middle Aged; D009200:Myocardial Contraction; D010455:Peptides; D011976:Receptors, Muscarinic / Q000276:immunology*
D001323:Autoantibodies; D015415:Biomarkers; D010455:Peptides; D011976:Receptors, Muscarinic; D000242:Cyclic AMP; D006152:Cyclic GMP