The melanocortin-4 receptor is expressed in enteroendocrine L cells and regulates the release of peptide YY and glucagon-like peptide 1 in vivo
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The melanocortin-4 receptor is expressed in enteroendocrine L cells and regulates the release of peptide YY and glucagon-like peptide 1 in vivo. / Panaro, Brandon L; Tough, Iain R; Engelstoft, Maja S; Matthews, Robert T; Digby, Gregory J; Møller, Cathrine L; Svendsen, Berit; Gribble, Fiona; Reimann, Frank; Holst, Jens Juul; Holst, Birgitte; Schwartz, Thue W; Cox, Helen M; Cone, Roger D.
In: Cell Metabolism, Vol. 20, No. 6, 02.12.2014, p. 1018-29.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The melanocortin-4 receptor is expressed in enteroendocrine L cells and regulates the release of peptide YY and glucagon-like peptide 1 in vivo
AU - Panaro, Brandon L
AU - Tough, Iain R
AU - Engelstoft, Maja S
AU - Matthews, Robert T
AU - Digby, Gregory J
AU - Møller, Cathrine L
AU - Svendsen, Berit
AU - Gribble, Fiona
AU - Reimann, Frank
AU - Holst, Jens Juul
AU - Holst, Birgitte
AU - Schwartz, Thue W
AU - Cox, Helen M
AU - Cone, Roger D
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/12/2
Y1 - 2014/12/2
N2 - 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 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.
AB - 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 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.
U2 - 10.1016/j.cmet.2014.10.004
DO - 10.1016/j.cmet.2014.10.004
M3 - Journal article
C2 - 25453189
VL - 20
SP - 1018
EP - 1029
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -
ID: 132047002