Protease-activated receptors: Regulation of neuronal function

Toshiyuki Saito, Nigel W. Bunnett

Research output: Contribution to journalReview articlepeer-review


Certain serine proteases from the circulation (e.g., coagulation factors), inflammatory cells (e.g., mast-cell tryptase, neutrophil proteinase 3), and from many other cell types (e.g., trypsins) can specifically signal to cells by cleaving protease-activated receptors (PARs), a family of four G protein-coupled receptors. Proteases cleave PARs at specific sites within the extracellular amino-terminus to expose amino-terminal tethered ligand domains that bind to and activate the cleaved receptors. The proteases that activate PARs are often generated and released during injury and inflammation, and activated PARs orchestrate tissue responses to injury, including hemostasis, inflammation, pain, and repair. This review concerns protease and PAR signaling in the nervous system. Neurons of the central and peripheral nervous systems express all four PARs. Proteases that may derive from the circulation, inflammatory cells, or neural tissues can cleave PARs on neurons and thereby activate diverse signaling pathways that control survival, morphology, release of neurotransmitters, and activity of ion channels. In this manner proteases and PARs regulate neurodegeneration, neurogenic inflammation, and pain transmission. Thus, PARs may participate in disease states and PAR antagonists or agonists may be useful therapies for certain disorders.

Original languageEnglish (US)
Pages (from-to)79-100
Number of pages22
JournalNeuroMolecular Medicine
Issue number1-2
StatePublished - Feb 2005


  • Hyperalgesia
  • Neurodegeneration
  • Neurogenic inflammation
  • Neuropeptides
  • Pain
  • Protease-activated receptors
  • Proteases

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience


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