Pharmacological characterization of the human 5-HT 4(d) receptor splice variant stably expressed in Chinese hamster ovary cells - Université Paris-Saclay Access content directly
Journal Articles British Journal of Pharmacology Year : 2000

Pharmacological characterization of the human 5-HT 4(d) receptor splice variant stably expressed in Chinese hamster ovary cells

Abstract

The recently identified C-terminal splice variant of the human 5-HT4 receptor, the h5-HT4(d) receptor, was stably expressed in a CHO cell line at 493±25 fmol mg−1 protein. We analysed its pharmacological properties by measuring binding affinities and 5-HT4 ligand-induced cyclic AMP production. The pharmacological binding profile determined in competition studies with the specific antagonist [3H]-GR113808 revealed a rank order of affinity of 5-HT4 ligands for the h5-HT4(d) receptor that was consistent with those previously reported for other 5-HT4 receptor isoforms. In adenylyl cyclase functional assays, the h5-HT4(d) receptor displayed equipotent coupling for all 5-HT4 agonists tested (EC50 in the range of 1–6 nM). EC50 values were lower than those previously obtained with the 5-HT4(e) receptor stably expressed in CHO cells indicating that the 5-HT4(d) receptor was more efficiently coupled to its effector than the 5-HT4(e) receptor isoform. Moreover, in terms of agonist efficacy (Emax), the benzamide derivative, renzapride displayed full agonist properties at the h5-HT4(d) receptor (same Emax as 5-HT) whereas it was previously shown to be a partial agonist at the h5-HT4(e) receptor. A constitutive activity of the h5-HT4(d) receptor was observed in CHO cells in the absence of any 5-HT4 ligand. Surprisingly, two 5-HT4 ligands, SB204070 and RS39604 which are described as highly potent antagonists in various biological models, revealed partial agonist properties at the h5-HT4(d) receptor. We conclude that C-terminal tails of 5-HT4 receptor isoforms may directly influence their functional properties.
Fichier principal
Vignette du fichier
Version HAL.pdf (361.69 Ko) Télécharger le fichier
Origin Files produced by the author(s)

Dates and versions

hal-03611636 , version 1 (17-03-2022)

Identifiers

Cite

Jeanne Mialet, Isabelle Berque-Bestel, Sames Sicsic, Michel Langlois, Rodolphe Fischmeister, et al.. Pharmacological characterization of the human 5-HT 4(d) receptor splice variant stably expressed in Chinese hamster ovary cells. British Journal of Pharmacology, 2000, 131 (4), pp.827-835. ⟨10.1038/sj.bjp.0703641⟩. ⟨hal-03611636⟩
14 View
16 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More