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| Research article summary (published 30 Dec 2002): |
The serotonin 5-HT4 receptor and the amyloid precursor protein processing.
Full Abstract
A large body of evidence supports a major role for the serotonin 5-HT(4) receptor in learning and memory and it is suggested that 5-HT(4) agonists may be beneficial for memory disorders such as Alzheimer's disease (AD). The 5-HT(4) receptors are members of the G protein-coupled receptor superfamily and are positively coupled to adenylyl cyclase. In this communication we show that a neuronal isoform of the human 5-HT(4) receptor, h5-HT(4(g)) regulates the metabolism of the amyloid precursor protein (APP695). This process is observed in Chinese hamster ovary (CHO) cells stably coexpressing the neuronal h5-HT(4(g)) receptor isoform as well as the human APP695. The 5-HT(4) agonists strongly stimulate the release of the non-amyloidogenic soluble amyloid precursor protein sAPPalpha as detected by immunoblot. Prucalopride was more potent than serotonin (5-HT) with regard to enhanced of sAPPalpha secretion. This process was blocked by a selective 5-HT(4) antagonist, GR113808. Furthermore, 5-HT(4) ligands enhance sAPPalpha secretion via cAMP-dependent and PKA-independent signalling pathways indicating there are alternative pathways by which the h5-HT(4) receptor via cAMP regulates APP metabolism. Because the alpha-cleavage event may preclude the formation of amyloidogenic peptides, and secreted sAPPalpha has putative neuroprotective and enhancing-memory properties, our present data suggest the 5-HT(4) receptor as a novel target for the treatment of AD.
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Author information
Author/s: Lezoualc'h, Frank (F); Robert, Sylvain J (SJ);
Affiliation: Cardiologie Cellulaire et Moléculaire INSERM U-446, Faculté de Pharmacie, Institut de Signalisation et Innovation Thérapeutique (IFR-75), Université Paris-Sud, F-9229, Châtenay-Malabry, France. frank.lezoualch@cep.u-psud.fr
Journal and publication information
Publication Type: Journal Article
Journal: Experimental gerontology (Exp Gerontol), published in England. (Language: eng)
Reference: -2003 Jan-Feb; vol 38 (issue 1-2) : pp 159-66
Dates: Created 2003/01/24; Completed 2003/05/12; Revised 2005/11/17;
PMID: 12543273, status: MEDLINE (last retrieval date: 11/6/2008)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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