Therapeutic Use of Muscarinic Acetylcholine Receptor Peptide to Prevent Mice Chagasic Cardiac Dysfunction

L. Sterin-Borda, L. Joensen, C. Bayo-Hanza, M. Esteva and E. Borda, Therapeutic Use of Muscarinic Acetylcholine Receptor Peptide to Prevent Mice Chagasic Cardiac Dysfunction. Journal of Molecular and Cellular Cardiology (2002) 34 , 1645–1654. Therapeutic use of a peptide corresponding to the aminoacid sequence of the second extracellular loop of human M 2 muscarinic acetylcholine receptor (M 2 mAChR peptide) was studied. Expression and biological activity of M 2 mAChR in association with circulating M 2 mAChR-related antibodies in cardiac tissue from chagasic mice were evaluated. Mice infected or not with trypomastigotes Tulahuen strain either treated or not treated with M 2 mAChR peptide were sacrificed at 8–9 weeks post-infection. Morphological, binding and contractility studies were performed on all animal groups. Hearts from infected mice showed a mAChR-related dysfunction, with a decrease in heart contractility, impaired response to exogenous mAChR agonist (carbachol) and a significant reduction of mAChR binding sites. Treating infected mice with M 2 mAChR peptide reversed those effects. Moreover, autoantibodies from infected mice recognized the M 2 mAChR peptide. In addition, serum from infected mice and the corresponding affinity purified IgG was capable of interacting with cardiac mAChR, reducing the number of binding sites and inhibiting the contractile response to exogenous agonist. In conclusion, (1) the development of alterations in mAChR related to cardiac dysfunction, may be associated with the presence of circulating antibodies against these receptors and (2) the chronic treatment with M 2 mAChR peptide prevented infected mice heart dysfunction. The mechanism could be explained by the ability of the M 2 mAChR peptide to inhibit the chronic interaction of autoantibodies specific to mAChR. The implication of M 2 mAChR peptide treatment in the host's immune response is discussed.