G-Protein–Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases

Meritxell Canals, Daniel P. Poole, Nicholas A. Veldhuis, Brian L. Schmidt, Nigel W. Bunnett

Research output: Contribution to journalReview articlepeer-review


G-protein–coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins. In the gastrointestinal tract, GPCRs expressed by epithelial cells sense contents of the lumen, and GPCRs expressed by epithelial cells, myocytes, neurons, and immune cells participate in communication among cells. GPCRs control digestion, mediate digestive diseases, and coordinate repair and growth. GPCRs are the target of more than one third of therapeutic drugs, including many drugs used to treat digestive diseases. Recent advances in structural, chemical, and cell biology research have shown that GPCRs are not static binary switches that operate from the plasma membrane to control a defined set of intracellular signals. Rather, GPCRs are dynamic signaling proteins that adopt distinct conformations and subcellular distributions when associated with different ligands and intracellular effectors. An understanding of the dynamic nature of GPCRs has provided insights into the mechanism of activation and signaling of GPCRs and has shown opportunities for drug discovery. We review the allosteric modulation, biased agonism, oligomerization, and compartmentalized signaling of GPCRs that control digestion and digestive diseases. We highlight the implications of these concepts for the development of selective and effective drugs to treat diseases of the gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)1600-1616
Number of pages17
Issue number6
StatePublished - May 2019


  • Drug Discovery
  • G Proteins
  • Receptors
  • Signal Transduction
  • Trafficking

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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