The melanocortin-4 receptor is expressed in enteroendocrine L cells and regulates the release of peptide YY and glucagon-like peptide 1 in vivo

TY - JOUR

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 - Summary 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 - Summary 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

SN - 1550-4131

VL - 20

SP - 1018

EP - 1029

JO - Cell Metabolism

JF - Cell Metabolism

IS - 6

ER -