RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives

Bioessays. 2016 Apr;38(4):344-54. doi: 10.1002/bies.201500118. Epub 2016 Jan 28.


Regulators of G protein signaling (RGS) proteins provide timely termination of G protein-coupled receptor (GPCR) responses. Serving as a central control point in GPCR signaling cascades, RGS proteins are promising targets for drug development. In this review, we discuss the involvement of RGS proteins in the pathophysiology of the gastrointestinal inflammation and their potential to become a target for anti-inflammatory drugs. Specifically, we evaluate the emerging evidence for modulation of selected receptor families: opioid, cannabinoid and serotonin by RGS proteins. We discuss how the regulation of RGS protein level and activity may modulate immunological pathways involved in the development of intestinal inflammation. Finally, we propose that RGS proteins may serve as a prognostic factor for survival rate in colorectal cancer. The ideas introduced in this review set a novel conceptual framework for the utilization of RGS proteins in the treatment of gastrointestinal inflammation, a growing major concern worldwide.

Keywords: GPCR signaling; RGS proteins; abdominal pain; cannabinoid receptors; gastrointestinal motility; inflammatory bowel disease; opioid receptors; serotonin receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Gastrointestinal Motility / drug effects
  • Gene Expression Regulation
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / physiopathology
  • Intestines / drug effects
  • Intestines / physiopathology
  • Mice
  • RGS Proteins / agonists
  • RGS Proteins / antagonists & inhibitors
  • RGS Proteins / genetics*
  • RGS Proteins / metabolism
  • Receptors, Cannabinoid / genetics
  • Receptors, Cannabinoid / metabolism
  • Receptors, Opioid / genetics
  • Receptors, Opioid / metabolism
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism
  • Signal Transduction
  • Small Molecule Libraries / therapeutic use
  • Visceral Pain / drug therapy*
  • Visceral Pain / genetics
  • Visceral Pain / metabolism
  • Visceral Pain / physiopathology


  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • RGS Proteins
  • Receptors, Cannabinoid
  • Receptors, Opioid
  • Receptors, Serotonin
  • Small Molecule Libraries