Conformational state of human cardiac 5-HT(4(g)) receptors influences the functional effects of polyclonal anti-5-HT(4) receptor antibodies.
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.
Di Scala
Emmanuella
E
UMR CNRS 6542, Physiologie des Cellules Cardiaques et Vasculaires, Faculté des Sciences et Techniques, Université François-Rabelais, Tours 37200, France.
Rose
Stéphanie
S
Hérault
Olivier
O
Argibay
Jorge
J
Cosnay
Pierre
P
Bozon
Véronique
V
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
D000906:Antibodies; D044422:Receptors, Serotonin, 5-HT4