Substance P activates Mas-related G protein-coupled receptors to induce itch

J Allergy Clin Immunol. 2017 Aug;140(2):447-453.e3. doi: 10.1016/j.jaci.2016.12.980. Epub 2017 Feb 20.

Abstract

Background: Substance P (SP) is linked to itch and inflammation through activation of receptors on mast cells and sensory neurons. There is increasing evidence that SP functions through Mas-related G protein-coupled receptors (Mrgprs) in addition to its conventional receptor, neurokinin-1.

Objective: Because Mrgprs mediate some aspects of inflammation that had been considered mediated by neurokinin-1 receptor (NK-1R), we sought to determine whether itch induced by SP can also be mediated by Mrgprs.

Methods: Genetic and pharmacologic approaches were used to evaluate the contribution of Mrgprs to SP-induced scratching behavior and activation of cultured dorsal root ganglion neurons from mice.

Results: SP-induced scratching behavior and activation of cultured dorsal root ganglion neurons was dependent on Mrgprs rather than NK-1R.

Conclusion: We deduce that SP activates MrgprA1 on sensory neurons rather than NK-1R to induce itch.

Keywords: Mas-related G protein–coupled receptors; Substance P; calcium imaging; dorsal root ganglion neurons; knockout mice; receptor antagonist.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Capsaicin / pharmacology
  • Cells, Cultured
  • Female
  • Ganglia, Spinal / cytology*
  • Humans
  • Male
  • Mice, Transgenic
  • Middle Aged
  • Pruritus / chemically induced
  • Pruritus / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, Neurokinin-1 / genetics
  • Sensory Receptor Cells / drug effects
  • Substance P
  • Young Adult

Substances

  • Receptors, G-Protein-Coupled
  • Receptors, Neurokinin-1
  • Substance P
  • Capsaicin