Protease-activated receptors: protease signaling in the gastrointestinal tract

Curr Opin Pharmacol. 2004 Dec;4(6):551-6. doi: 10.1016/j.coph.2004.08.004.


Serine proteases from the circulation, inflammatory cells, digestive glands and microorganisms can signal to cells by cleaving protease-activated receptors (PARs), a family of four G-protein-coupled receptors. Proteases cleave PARs at specific sites to expose tethered ligand domains that bind to and activate the cleaved receptors. Despite this irreversible mechanism of activation, PAR signaling is tightly regulated to prevent the uncontrolled stimulation of cells. Although PARs are found in all organ systems, protease signaling is of particular interest in the gastrointestinal tract, where proteases regulate neurotransmission, secretion, motility, epithelial permeability and intestinal inflammation, and can thus contribute to disease.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / microbiology
  • Gastrointestinal Tract / physiology*
  • Humans
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / physiopathology
  • Models, Biological
  • Receptors, Proteinase-Activated / drug effects
  • Receptors, Proteinase-Activated / physiology*
  • Serine Endopeptidases / pharmacology
  • Serine Endopeptidases / physiology*
  • Signal Transduction / drug effects*


  • Receptors, Proteinase-Activated
  • Serine Endopeptidases