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Conformational state of human cardiac 5-HT4(g) receptors influences the functional effects of polyclonal anti-5-HT4 receptor antibodies

Abstract : 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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https://hal.inrae.fr/hal-03170843
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Submitted on : Tuesday, March 16, 2021 - 2:51:42 PM
Last modification on : Friday, April 9, 2021 - 12:54:06 PM

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Emmanuella Di Scala, Stéphanie Rose, Olivier Hérault, Jorge Argibay, Pierre Cosnay, et al.. Conformational state of human cardiac 5-HT4(g) receptors influences the functional effects of polyclonal anti-5-HT4 receptor antibodies. Biochemical Pharmacology, Elsevier, 2007, 73 (7), pp.964-971. ⟨10.1016/j.bcp.2006.12.009⟩. ⟨hal-03170843⟩

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