title: Agonist-like activity of antibodies directed against the second extracellular loop of the human cardiac serotonin 5-HT4(e) receptor in transfected COS-7 cells.
abstract: We have previously reported that antipeptide antibodies directed against the second extracellular loop of the cardiac h5-HT4 receptor could block the activation of the L-type Ca channel in human atrial cardiomyocytes. In this paper we investigate the immunological and physiological activity of these antibodies, in a cell system expressing a larger amount of receptors than the atrial cells. The recombinant receptor was expressed at the surface of COS-7 cells under an active form (serotonin, EC50 = 1.81 x 10(-7) M), at a high level (375 +/- 25 fmol receptor/mg total protein) and was able to bind a specific ligand (GR113808) with a high affinity (Kd = 0.28 +/- 0.05 nM). In this system, the same anti-peptide antibodies used for the cardiac cells induced an "agonist-like" effect on the recombinant h5-HT4 receptor. These results are in line with those shown for others G-protein coupled receptors, as adrenoreceptors. In addition, this work showed that the effect of the antibodies is not only dependent on the epitopic region recognised but also on the molecular density and/or the cellular environment of the target receptors. Finally, our results support the hypothesis that the h5-HT4 receptor could be a new target for autoantibodies in patients with atrial arrhythmia.
authors.affiliation: CNRS-UMR 6542, Physiologie des Cellules Cardiaques et Vasculaires, Faculté des Sciences et Techniques, Parc de Grandmont, 37200 Tours, France. bozon@univ-tours.fr
authors.forename: V
authors.initials: V
authors.lastname: Bozon
authors.forename: E
authors.initials: E
authors.lastname: Di Scala
authors.forename: P
authors.initials: P
authors.lastname: Eftekhari
authors.forename: J
authors.initials: J
authors.lastname: Hoebeke
authors.forename: F
authors.initials: F
authors.lastname: Lezoualc'h
authors.forename: R
authors.initials: R
authors.lastname: Fischmeister
authors.forename: J
authors.initials: J
authors.lastname: Argibay
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity; D001281:Atrial Fibrillation / Q000209:etiology / Q000276:immunology; D001323:Autoantibodies; D019556:COS Cells; D004789:Enzyme Activation; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D044422:Receptors, Serotonin, 5-HT4; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D044422:Receptors, Serotonin, 5-HT4; D000262:Adenylyl Cyclases