Format

Send to

Choose Destination
Mol Metab. 2018 Jun;12:62-75. doi: 10.1016/j.molmet.2018.03.016. Epub 2018 Apr 3.

Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms.

Author information

1
Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Nørre Allé 14, 2200, Copenhagen, Denmark. Electronic address: Egerod@sund.ku.dk.
2
Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Nørre Allé 14, 2200, Copenhagen, Denmark.
3
Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genomics, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Allé 14, 2200, Copenhagen, Denmark.
4
Department of Neuroscience, University of Copenhagen, Nørre Allé 14, 2200, Copenhagen, Denmark.
5
Department of Biochemistry, UT Southwestern Medical Center at Dallas, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
6
Division of Hypothalamic Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA. Electronic address: Laurent.gautron@UTSouthwestern.edu.

Abstract

OBJECTIVES:

G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract.

METHODS:

Using a combination of high-throughput quantitative PCR, RNA sequencing, and in situ hybridization, we systematically quantified GPCRs expressed in vagal unmyelinated Nav1.8-expressing afferents.

RESULTS:

GPCRs for gut hormones that were the most enriched in Nav1.8-expressing vagal unmyelinated afferents included NTSR1, NPY2R, CCK1R, and to a lesser extent, GLP1R, but not GHSR and GIPR. Interestingly, both GLP1R and NPY2R were coexpressed with CCK1R. In contrast, NTSR1 was coexpressed with GPR65, a marker preferentially enriched in intestinal mucosal afferents. Only few microbiome-derived metabolite sensors such as GPR35 and, to a lesser extent, GPR119 and CaSR were identified in the Nav1.8-expressing vagal afferents. GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Nav1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents.

CONCLUSION:

Overall, this study provides a comprehensive description of GPCR-dependent sensing mechanisms in vagal afferents, including novel coexpression patterns, and conceivably coaction of key receptors for gut-derived molecules involved in gut-brain communication.

KEYWORDS:

G protein-coupled receptors; GLP1R; Gut hormones; Gut-brain axis; NTSR1; Vagal afferent nerves

PMID:
29673577
PMCID:
PMC6001940
DOI:
10.1016/j.molmet.2018.03.016
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center