title: Effects on heart rate of an anti-M2 acetylcholine receptor immune response in mice.
abstract: Autoantibodies in vitro modulating the M2 acetylcholine receptor (M2ACh-R) were observed in patients with idiopathic dilated cardiomyopathy (IDC) or Chagas' cardiomyopathy (ChC). We investigated the in vivo consequences on heart rate of such antibodies in mice immunized with a peptide derived from the second extracellular loop of the M2ACh-R compared with mice immunized with an irrelevant peptide. Sera of mice immunized with the M2ACh-R-derived peptide recognized the M2ACh-R on immunoblots and enhanced agonist activity of carbachol toward the M2AChR transfected in CHO cells. In vivo, no difference could be shown in heart rate or heart rate variability between the two groups of mice. The decrease in heart rate induced by carbachol was more pronounced, however, in the M2ACh-R immunized mice. The increase in heart rate induced by atropine, gallamine, and isoproterenol was significantly attenuated in the M2ACh-R immunized mice. Analysis of heart rate variability further argued for an increased parasympathetic response to different drugs in the M2ACh-R immunized mice. Antibodies raised against the M2AChR can behave as positive M2AChR allosteric modulators in vivo. They might be protective in boosting the activity of the parasympathetic drive to the heart, especially in patients with a high sympathetic tone.
authors.affiliation: C.N.R.S, UPR 9021, IBMC, Laboratory of Immunological and Therapeutical Chemistry, Strasbourg, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Peter
authors.forename: Jean
authors.initials: J
authors.lastname: Tugler
authors.forename: Pierre
authors.initials: P
authors.lastname: Eftekhari
authors.forename: Damien
authors.initials: D
authors.lastname: Maurice
authors.forename: Johan
authors.initials: J
authors.lastname: Hoebeke
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Roegel
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology* / Q000502:physiology; D001285:Atropine / Q000494:pharmacology; D016466:CHO Cells; D002217:Carbachol / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000032:analysis; D004562:Electrocardiography; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007114:Immunization; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010275:Parasympathetic Nervous System / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D043585:Receptor, Muscarinic M2 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014162:Transfection
chemical_list: D000906:Antibodies; D010446:Peptide Fragments; D043585:Receptor, Muscarinic M2; D001285:Atropine; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol; D005703:Gallamine Triethiodide