Neuropeptide S Receptor Induces Neuropeptide Expression and Associates With Intermediate Phenotypes of Functional Gastrointestinal Disorders (Gastroenterology 2010;138:98-107)

Abstract

Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder, of largely unknown etiology and pathobiology. There is growing evidence regarding the genetic contribution in IBS, however the precise etiology of IBS is still unknown. Recently, it has been proposed that several genetic markers are associated with some aspect of IBS. Neuropeptide S receptor 1 (NPSR1), the receptor for neuropeptide S (NPS), is expressed on the intestinal epithelium, and is involved in inflammation, anxiety, and nociception. NPSR1 gene was recently found to be genetically associated with inflammatory bowel disease and asthma.1,2 The author wanted to determine whether NPS induces expression of gastrointestinal (GI) neuropeptides; and to associate NPSR1 single nucleotide polymorphisms (SNPs) with symptom phenotype and GI functions in health and functional GI disorders (FGID). The author undertook the present study in vitro and in vivo model together. First, the effect of NPS on messenger RNA expression of neuropeptides was assessed in NPSR1-tranfected HEK293 cells. Second, 17 NPSR1 polymorphisms were compared between 466 FGID patients and 233 healthy controls. They showed that NPS-NPSR1 signaling induced increased expressions of cholecystokinin, vasoactive intestinal peptide, peptide YY, and somatostatin. There were no significant associations with phenotypes of FGID symptoms. However, there were several NPSR1 SNPs associated with individual motor or sensory functions; the associations of SNPs rs2609234, rs6972158, and rs1379928 with colonic transit rate, while the rs1379928 polymorphism was also associated with pain, gas, and urgency sensory ratings at 36 mm Hg distention. The author concluded that the expression of several neuropeptides is induced upon NPS-NPSR1 signaling and NPSR1 variants are associated with colonic transit in FGID.