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.

We have previously reported that antipeptide antibodies directed against the second extracellular loop of the cardiac h5-HT 4 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, EC 50 = 1.81 2 10 m 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-HT 4 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 epit...