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Molecular and functional characterization of a 5‐HT 4 receptor cloned from human atrium
Author(s) -
Blondel Olivier,
Vandecasteele Grégoire,
Gastineau Monique,
Leclerc Stéphanie,
Dahmoune Yamina,
Langlois Michel,
Fischmeister Rodolphe
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00820-x
Subject(s) - 5 ht4 receptor , receptor , atrium (architecture) , agonist , chronotropic , biology , stimulation , medicine , endocrinology , biochemistry , atrial fibrillation , heart rate , blood pressure
5‐Hydroxytryptamine (5‐HT) has been shown to exert positive inotropic, chronotropic, and lusitropic effects and to stimulate the L‐type calcium channel current ( I Ca ) in human atrial tissue through activation of the pharmacologically defined 5‐HT 4 receptor subtype. However, the molecular nature of the receptor(s) involved in these effects is still unknown. In the present study, we report the molecular nature of a 5‐HT 4 receptor cloned from human atrium, h5‐HT 4A . Sequence analysis reveals that h5‐HT 4A displays a 93% protein identity with the short form of the 5‐HT 4 receptor recently isolated from rat brain. h5‐HT 4A mRNA is expressed in human atrium but not ventricle, and is also found in brain and GI tract. h5‐HT 4A transiently expressed in COS‐7 cells displays a classical 5‐HT 4 pharmacological profile. However, affinities of the h5‐HT 4A receptor for agonists such as ML10302, BIMU1, renzapride or zacopride were 4–10‐fold lower than the ones found in brain. Moreover, the stimulatory patterns of cAMP formation by h5‐HT 4A in response to the 5‐HT 4 agonists ML10302 and renzapride were very similar to the patterns of stimulation of I Ca obtained in response to these compounds in human atrial myocytes. We conclude that h5‐HT 4A likely mediates the effects of 5‐HT in human atrium and may differ from 5‐HT 4 receptor isoforms present in the brain and GI tract.