Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction
Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulati...
Guardado en:
| Autores principales: | , , , , , , , , , |
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| Formato: | Articulo Preprint |
| Lenguaje: | Inglés |
| Publicado: |
2015
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/98736 https://ri.conicet.gov.ar/11336/53970 https://pubs.acs.org/doi/10.1021/cn500318q |
| Aporte de: |
| id |
I19-R120-10915-98736 |
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| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Biología Food intake Ghrelin Growth hormone secretagogue receptor Lorcaserin Serotonin 2C receptor |
| spellingShingle |
Ciencias Médicas Biología Food intake Ghrelin Growth hormone secretagogue receptor Lorcaserin Serotonin 2C receptor Schellekens, Harriët De Francesco, Pablo Nicolás Kandil, Dalia Theeuwes, Wessel F. McCarthy, Triona Van Oeffelen, Wesley E. P. A. Perello, Mario Giblin, Linda Dinan, Timothy G. Cryan, John F. Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction |
| topic_facet |
Ciencias Médicas Biología Food intake Ghrelin Growth hormone secretagogue receptor Lorcaserin Serotonin 2C receptor |
| description |
Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghreliņs orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghreliņs orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management. |
| format |
Articulo Preprint |
| author |
Schellekens, Harriët De Francesco, Pablo Nicolás Kandil, Dalia Theeuwes, Wessel F. McCarthy, Triona Van Oeffelen, Wesley E. P. A. Perello, Mario Giblin, Linda Dinan, Timothy G. Cryan, John F. |
| author_facet |
Schellekens, Harriët De Francesco, Pablo Nicolás Kandil, Dalia Theeuwes, Wessel F. McCarthy, Triona Van Oeffelen, Wesley E. P. A. Perello, Mario Giblin, Linda Dinan, Timothy G. Cryan, John F. |
| author_sort |
Schellekens, Harriët |
| title |
Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction |
| title_short |
Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction |
| title_full |
Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction |
| title_fullStr |
Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction |
| title_full_unstemmed |
Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction |
| title_sort |
ghrelińs orexigenic effect is modulated via a serotonin 2c receptor interaction |
| publishDate |
2015 |
| url |
http://sedici.unlp.edu.ar/handle/10915/98736 https://ri.conicet.gov.ar/11336/53970 https://pubs.acs.org/doi/10.1021/cn500318q |
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