P2Y1, P2Y2, and TRPV1 Receptors Are Increased in Diarrhea-Predominant Irritable Bowel Syndrome and P2Y2 Correlates with Abdominal Pain

Dig Dis Sci. 2016 Oct;61(10):2878-2886. doi: 10.1007/s10620-016-4211-5. Epub 2016 Jun 1.

Abstract

Background: Previous studies indicated that P2Y1 and P2Y2 receptors, which are widely distributed in the enteric nervous system, are related to pain, while TRPV1 may contribute to visceral pain and hypersensitivity states in irritable bowel syndrome (IBS). Other studies showed that ATP activates the capsaicin-sensitive TRPV1 channel via P2Y receptors.

Aim: To detect the expression of P2Y1, P2Y2, and TRPV1 receptors in diarrhea-predominant IBS (IBS-D) patients and analyze any correlations with abdominal pain and to investigate interactions between P2Y receptors and the TRPV1 receptor in IBS-D patients.

Methods: Rectosigmoid biopsies were collected from patients with IBS-D (n = 36) and healthy controls (n = 15). Abdominal pain was scored using a 10-cm visual analogue scale. Expression levels of P2Y1, P2Y2, and TRPV1 receptors in rectosigmoid biopsies were determined by real-time PCR and double-labeling immunofluorescence with specific antibodies.

Results: Both mRNA and protein expression levels of P2Y1, P2Y2, and TRPV1 receptors were increased in IBS-D compared with controls. Of these receptors, P2Y2 expression correlated with the maximum pain scores (p = 0.02, r = 0.63, Spearman correlation) in IBS-D patients. However, no relationships were detected between P2Y receptors and the TRPV1 receptor.

Conclusion: In the present study, we identified an increased expression of P2Y1 and P2Y2 receptors in the rectosigmoid mucosa of IBS-D patients, and P2Y2 correlated with abdominal pain. Furthermore, we identified an increase in TRPV1 expression; however, there were no correlations found between P2Y receptors and the TRPV1 receptor.

Keywords: Abdominal pain; Irritable bowel syndrome; Purinergic receptor P2Y1; Purinergic receptor P2Y2; TRPV1 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / etiology
  • Abdominal Pain / genetics*
  • Adult
  • Aged
  • Biopsy
  • Colon, Sigmoid / metabolism*
  • Colon, Sigmoid / pathology
  • Diarrhea / etiology
  • Diarrhea / genetics*
  • Female
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Irritable Bowel Syndrome / complications
  • Irritable Bowel Syndrome / genetics*
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Purinergic P2Y1 / genetics*
  • Receptors, Purinergic P2Y2 / genetics*
  • Rectum / metabolism*
  • Rectum / pathology
  • TRPV Cation Channels / genetics*

Substances

  • RNA, Messenger
  • Receptors, Purinergic P2Y1
  • Receptors, Purinergic P2Y2
  • TRPV Cation Channels
  • TRPV1 protein, human