Neuropharmacology and NeurotoxicologyCloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclaseClaeysen, Sylvie1; Faye, Patrick1; Sebben, Michèle1; Lemaire, Stéphanie2; Bockaert, Joël1,3; Dumuis, Aline1Author Information 1CNRS UPR 9023, Centre CNRS-INSERM de Pharmacologie-Endocrinologie (CCIPE), 141 rue de la Cardonille, 34094 Montpellier cedex 05 2CRBM du CNRS, UPR 9008, INSERM U.249, 1919 route de Mende, BP 5051, 34033 Montpellier Cedex 1, France 3Corresponding Author: Joël Bockaert ACKNOWLEDGEMENTS: We are grateful to Dr Christophe Gerald (Synaptic Pharmaceutical Corporation, Paramus NJ, USA) for the generous gift of rat 5-HT4L and 5-HT4S cDNA. For helpful comments and valuable discussions we thank Drs L. Fagni and J.-P. Pin. Mrs A.L. Turner-Madeuf and M. Passama are acknowledged for their help in language revision and preparation of figures respectively. This work was supported by grants from the Centre National de la Recherche Scientifique Laboratoires Fournier-Debat (Daix, France) and the Fondation pour la Recherche Medicale. Website publication 24 September 1997 Received 15 July 1997; accepted 5 August 1997 NeuroReport: October 20th, 1997 - Volume 8 - Issue 15 - p 3189-3196 Buy Abstract WE have isolated a cDNA encoding the 5-HT4S receptor by RT-PCR on poly (A)+ RNA from both human heart and brain. The sequence homology with the rat and mouse 5-HT4 receptors was high: 93.8% of identity in the amino acid sequence. None of the 24 amino acid substitutions observed between rat and human receptors are at positions likely to modify their pharmacology. Comparing the pharmacological properties of six agonists and five antagonists on rat and human 5-HT4S receptors revealed no significant differences. We have analyzed the behavior of renzapride, a full and a partial agonist on mouse colliculi neurons and human heart biological responses respectively. The coupling efficiency of renzapride was two-fold lower than that of 5-HT for the stimulation of 5-HT4S receptors transfected in two different cell lines (LLC-PK1 and COS-7), but increasing the receptor density suppressed the partial agonist effect of renzapride. © Lippincott-Raven Publishers.