Abstract
The proglucagon-derived peptide glucagon-like peptide 2 (GLP-2), a product of a subset of gut epithelial cells, is pursued clinically for its ability to stimulate gut epithelial growth and repair. Here we show that although specific epithelial progenitors respond to GLP-2 administration, the epithelium does not express the GLP-2 receptor. Rather, enteric neurons express the receptor, respond to GLP-2, and transmit a signal (which can be blocked by the voltage-gated sodium channel inhibitor tetrodotoxin) back to the epithelium. Thus the nervous system is a key component of a feedback loop regulating epithelial growth and repair.