Inhibitory activity of antibodies against the human atrial 5-HT(4)receptor.
Antibodies directed against the second extracellular loop of G protein-coupled receptors have been shown to exert "agonist-like" activities. In order to test the hypothesis that this is a general phenomenon, antibodies were raised in rabbits against a synthetic peptide corresponding to the second extracellular loop of the newly sequenced human cardiac 5-HT(4)receptor. The antibodies were affinity-purified and shown to recognize the 5-HT(4)receptor in immunoblots of Chinese hamster ovary (CHO) cells expressing the receptor. The antibodies had no intrinsic effect but could depress the activation of L -type calcium channel induced by serotonin in human atrial cells. This antagonist-like effect was exerted both by intact IgG and by Fab fragments. These results are physiologically important since it has been shown that the 5-HT(4)receptor could be a target for autoantibodies in mothers at risk of giving birth to children with neonatal atrio-ventricular block.
Sallé
L
L
Faculté des Sciences, Physiologie des Cellules Cardiaques et Vasculaires, 37200 Tours, France.
Eftekhari
P
P
Aupart
M
M
Cosnay
P
P
Hoebeke
J
J
Argibay
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D016275:Atrial Function; D016466:CHO Cells; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D004594:Electrophysiology; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000276:immunology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000276:immunology / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D011985:Receptors, Serotonin; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin