期刊
CELL METABOLISM
卷 20, 期 6, 页码 1018-1029出版社
CELL PRESS
DOI: 10.1016/j.cmet.2014.10.004
关键词
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资金
- NIH [R24DK096527, RO1DK070332]
- Novo Nordisk Foundation
- Vanderbilt Diabetes Research and Training Center [DK20593]
- Digestive Disease Research Center [P30DK058404]
- [WT088357/Z/09/Z]
- [WT084210/Z/07/Z]
- Medical Research Council [MC_UU_12012/3, MC_UU_12012/5/B] Funding Source: researchfish
- MRC [MC_UU_12012/3] Funding Source: UKRI
The 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 alpha-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.
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