The Melanocortin-4 Receptor Is Expressed in Enteroendocrine L Cells and Regulates the Release of Peptide YY and Glucagon-like Peptide 1 In Vivo
| Autor: | Frank Reimann, Roger D. Cone, Helen M. Cox, Cathrine Laustrup Møller, Gregory J. Digby, Jens J. Holst, Birgitte Holst, Brandon L. Panaro, Thue W. Schwartz, Iain R. Tough, Robert T. Matthews, Fiona M. Gribble, Maja S. Engelstoft, Berit Svendsen |
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| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Colon Physiology Enteroendocrine Cells Mice Transgenic Enteroendocrine cell Biology Peptides Cyclic Article Mice 03 medical and health sciences Paracrine signalling 0302 clinical medicine Intestinal mucosa Glucagon-Like Peptide 1 Internal medicine medicine Acids Heterocyclic Animals Humans Peptide YY Receptor Molecular Biology 030304 developmental biology Oxadiazoles 0303 health sciences digestive oral and skin physiology Cell Biology Immunohistochemistry Mice Inbred C57BL Melanocortin 4 receptor Endocrinology Receptor Melanocortin Type 4 Melanocortin Gastrointestinal function hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
| Zdroj: | Cell Metabolism. 20(6):1018-1029 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2014.10.004 |
| Popis: | SummaryThe melanocortin-4 receptor (MC4R) is expressed in the brainstem and vagal afferent nerves and regulates a number of aspects of gastrointestinal function. Here we show that the receptor is also diffusely expressed in cells of the gastrointestinal system, from stomach to descending colon. Furthermore, MC4R is the second most highly enriched GPCR in peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) expressing enteroendocrine L cells. When vectorial ion transport is measured across mouse or human intestinal mucosa, administration of α-MSH induces a MC4R-specific PYY-dependent antisecretory response consistent with a role for the MC4R in paracrine inhibition of electrolyte secretion. Finally, MC4R-dependent acute PYY and GLP-1 release from L cells can be stimulated in vivo by intraperitoneal (i.p.) administration of melanocortin peptides to mice. This suggests physiological significance for MC4R in L cells and indicates a previously unrecognized peripheral role for the MC4R, complementing vagal and central receptor functions. |
| Databáze: | OpenAIRE |
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