INTERACTION OF CHAGASIC AUTOANTIBODIES WI TH THE 3RD 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 th ird extracellular domain of human muscarinic acetylcholine receptors b y using a synthetic peptide corresponding to the sequence 169-192 of t he receptor. Immunoaffinity purified antipeptide antibodies displayed cardiac muscarinic activity as decreased contractility and cAMP produc tion and increased cGMP levels. These effects were specifically blocke d by the synthetic peptide and by atropine. A strong association betwe en the existence of circulating autoantibodies and the presence of dys autonomia was shown, making these autoantibodies an appropriate marker of heart autonomic dysfunction.