Conformational state of human cardiac 5-HT4(g) receptors influences the functional effects of polyclonal anti-5-HT4 receptor antibodies
2007
Di Scala, Emmanuella | Rose, Stéphanie | Hérault, Olivier | Argibay, Jorge | Cosnay, Pierre | Bozon, Véronique
The functional effects of the anti-G21V antibody directed against the second extracellular loop of human heart S-HT4 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-HT4(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-HT4(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-HT4(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 hS-HT4(g) receptor density. Inhibition of either phosphodiesterases or Gi proteins had no effect upon the action of the antibody. Conformational states of the 5-HT4 receptor and/or equilibrium between different states of receptors may then determine the functional effect of antibodies against this receptor. (c) 2006 Elsevier Inc. All rights reserved.
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