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http://hdl.handle.net/10261/63593
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Zugaza, José L. | - |
dc.date.accessioned | 2012-12-26T10:19:31Z | - |
dc.date.available | 2012-12-26T10:19:31Z | - |
dc.date.issued | 2001 | - |
dc.identifier | doi: 10.1074/jbc.M109008200 | - |
dc.identifier | issn: 0021-9258 | - |
dc.identifier | e-issn: 1083-351X | - |
dc.identifier.citation | Journal of Biological Chemistry 276(48): 44881-4888 (2001) | - |
dc.identifier.uri | http://hdl.handle.net/10261/63593 | - |
dc.description.abstract | The serotonin 5-HT4 receptor has recently gained a lot of attention for its functional roles in central processes such as memory and cognition. In this study, we show that activation of the human 5-HT4 (h5-HT4) receptor stimulates the secretion of the non-amyloidogenic soluble form of the amyloid precursor protein (sAPPα). 5-HT enhanced the level of secreted sAPPα in a time- and dose-dependent manner in Chinese hamster ovary cells stably expressing the h5-HT4(e) receptor isoform. The increase was inhibited by the selective 5-HT4 receptor antagonist, GR113808. The 5-HT4 selective agonists, prucalopride and renzapride, also increased secreted sAPPα in IMR32 human neuroblastoma cells. The stimulatory effect of 5-HT was mimicked by forskolin, a direct activator of adenylyl cyclase, and 8-bromo-cAMP, a membrane-permeant cAMP analogue. On the contrary, inhibition of protein kinase A (PKA) by H89 potentiated the 5-HT-induced increase in both secreted and cellular sAPPα. This phenomenon involves a novel PKA-independent stimulatory process that overcomes a PKA-dependent inhibitory one. Finally, activation of the h5-HT 4(e) receptor did not modify extracellular amyloid β-protein in Chinese hamster ovary cells transfected with the human APP695. Given the neuroprotective and enhancing memory effects of sAPPα, our results may open a new avenue for the treatment of Alzheimer's disease. | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.rights | closedAccess | - |
dc.title | The Human Serotonin 5-HT4 Receptor Regulates Secretion of Non-amyloidogenic Precursor Protein | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1074/jbc.M109008200 | - |
dc.date.updated | 2012-12-26T10:19:31Z | - |
dc.description.version | Peer Reviewed | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.grantfulltext | none | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
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accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
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