Molecular metabolismApr 21, 2018

Mapping receptors in vagus nerve sensory fibers reveals new ways the gut communicates with the brain

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 1, 2026

Abstract

The expression profile of G protein-coupled receptors (GPCRs) in mouse vagal unmyelinated afferents reveals significant enrichment of specific receptors for gut hormones.

NTSR1, NPY2R, and CCK1R are the most enriched GPCRs in Na1.8-expressing vagal unmyelinated afferents, indicating a strong link to gut hormone signaling.
Coexpression of GLP1R and NPY2R with CCK1R suggests potential interactions among these receptors in gut-brain communication.
Few microbiome-derived metabolite sensors, such as GPR35, were identified, suggesting limited representation of gut microbial signaling in vagal afferents.
GPCRs associated with lipid sensing, inflammation, and neurotransmitter signaling were also highly present, indicating diverse sensory mechanisms in these neurons.
A total of 21 orphan GPCRs with unknown functions were identified, pointing to unexplored signaling pathways in vagal afferents.

Simplified

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 Na1.8-expressing afferents. v

RESULTS: GPCRs for gut hormones that were the most enriched in Na1.8-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 Na1.8-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 Na1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents. v v v

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.

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Mapping receptors in vagus nerve sensory fibers reveals new ways the gut communicates with the brain

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief