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Protease-Activated Receptors and Itch

  • Chapter
Pharmacology of Itch

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 226))

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 itch-signaling pathway are good targets to develop novel treatments for most types of chronic itch that are poorly treated with antihistamines.

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Abbreviations

ACC:

Anterior cingulate cortex

AYPGKF:

Ala-Tyr-Pro-Gly-Lys-Phe-NH2

BAM8-22:

Bovine adrenal medulla 8-22

KLK:

Kallikrein

Mrgpr:

Mas-related G-protein-coupled receptors

NGF:

Nerve growth factor

PARs:

Protease-activated receptors

PCC:

Posterior cingulate cortex

PLC:

Phospholipase C

SLIGRL:

Ser-Leu-Ile-Gly-Arg-Leu-NH2

spink5 :

serine protease inhibitor Kazal type 5

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Acknowledgments

The work was supported by grants from the National Institutes of Health DE013685, AR057194, and AR063228.

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Authors and Affiliations

  1. Department of Dermatology, Anatomy and Cell Biology/Temple Itch Center, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    Tasuku Akiyama

  2. Department of Dermatology/Cutaneous Biology Research Center, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, Boston, MA, 02129, USA

    Ethan A. Lerner

  3. Department of Neurobiology, Physiology and Behavior, University of California, Davis, 1 Shields Avenue, Davis, CA, 95616, USA

    E. Carstens

Authors
  1. Tasuku Akiyama
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  2. Ethan A. Lerner
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  3. E. Carstens
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Corresponding authors

Correspondence to Ethan A. Lerner or E. Carstens .

Editor information

Editors and Affiliations

  1. Department of Pharmacology Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

    Alan Cowan

  2. Department of Dermatology, Temple University School of Medicine, Philadephia, Pennsylvania, USA

    Gil Yosipovitch

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© 2015 Springer-Verlag Berlin Heidelberg

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Akiyama, T., Lerner, E.A., Carstens, E. (2015). Protease-Activated Receptors and Itch. In: Cowan, A., Yosipovitch, G. (eds) Pharmacology of Itch. Handbook of Experimental Pharmacology, vol 226. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44605-8_13

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