title: Conformational state of human cardiac 5-HT(4(g)) receptors influences the functional effects of polyclonal anti-5-HT(4) receptor antibodies.
abstract: The functional effects of the anti-G21V antibody directed against the second extracellular loop of human heart 5-HT(4) receptors can differ when the receptors are expressed in different cell lines. Here, we extend these studies to show variation in the responses of 5-HT(4(g)) receptors to the antibody within the same expression system. In a previous report no effect of the anti-G21V antibodies had been shown upon 5-HT(4(g)) receptors expressed in CHO cells. Here the same antibodies alone or when added before 5-HT had a functional "inverse-agonist like" effect upon 5-HT(4(g)) receptors expressed in a separate line of CHO cells. Although these CHO cells showed a lower efficacy of cAMP production evoked by 5-HT than the previous report they express a similar h5-HT(4(g)) receptor density. Inhibition of either phosphodiesterases or Gi proteins had no effect upon the action of the antibody. Conformational states of the 5-HT(4) receptor and/or equilibrium between different states of receptors may then determine the functional effect of antibodies against this receptor.
authors.affiliation: UMR CNRS 6542, Physiologie des Cellules Cardiaques et Vasculaires, Faculté des Sciences et Techniques, Université François-Rabelais, Tours 37200, France.
authors.forename: Emmanuella
authors.initials: E
authors.lastname: Di Scala
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rose
authors.forename: Olivier
authors.initials: O
authors.lastname: Hérault
authors.forename: Jorge
authors.initials: J
authors.lastname: Argibay
authors.forename: Pierre
authors.initials: P
authors.lastname: Cosnay
authors.forename: Véronique
authors.initials: V
authors.lastname: Bozon
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D009206:Myocardium / Q000737:chemistry*; D011487:Protein Conformation; D044422:Receptors, Serotonin, 5-HT4 / Q000737:chemistry* / Q000276:immunology
chemical_list: D000906:Antibodies; D044422:Receptors, Serotonin, 5-HT4