Protease-activated receptors and itch

Tasuku Akiyama, Ethan A. Lerner, E. Carstens

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Protease-activated receptors (PARs) have been implicated in a variety of physiological functions, as well as somatosensation and particularly itch and pain. Considerable attention has focused on PARs following the finding they are upregulated in the skin of atopic dermatitis patients. The present review focuses on recent studies showing that PARs are critically involved in itch and sensitization of itch. PARs are expressed by diverse cell types including primary sensory neurons, keratinocytes, and immune cells and are activated by proteases that expose a tethered ligand. Endogenous proteases are also released from diverse cell types including keratinocytes and immune cells. Exogenous proteases released from certain plants and insects contacting the skin can also induce itch. Increased levels of proteases in the skin contribute to inflammation that is often accompanied by chronic itch which is not predominantly mediated by histamine. The neural pathway signaling itch induced by activation of PARs is distinct from that mediating histamine-induced itch. In addition, there is evidence that PARs play an important role in sensitization of itch signaling under conditions of chronic itch. These recent findings suggest that PARs and other molecules involved in the itchsignaling pathway are good targets to develop novel treatments for most types of chronic itch that are poorly treated with antihistamines.

Original languageEnglish (US)
Pages (from-to)219-235
Number of pages17
JournalHandbook of Experimental Pharmacology
Volume226
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Proteinase-Activated Receptors
Peptide Hydrolases
Skin
Keratinocytes
Histamine
Neural Pathways
Histamine Antagonists
Sensory Receptor Cells
Atopic Dermatitis
Neurons
Insects
Chemical activation
Ligands
Inflammation
Pain
Molecules

Keywords

  • Brain
  • GPCR
  • Human
  • Mouse
  • Pain
  • Pruritus
  • Rat
  • Scratching
  • Spinal cord

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Protease-activated receptors and itch. / Akiyama, Tasuku; Lerner, Ethan A.; Carstens, E.

In: Handbook of Experimental Pharmacology, Vol. 226, 01.01.2015, p. 219-235.

Research output: Contribution to journalArticle

Akiyama, Tasuku ; Lerner, Ethan A. ; Carstens, E. / Protease-activated receptors and itch. In: Handbook of Experimental Pharmacology. 2015 ; Vol. 226. pp. 219-235.
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