title: Substance P activates Mas-related G protein-coupled receptors to induce itch.
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.
  
  
  CONCLUSIONS
  We deduce that SP activates MrgprA1 on sensory neurons rather than NK-1R to induce itch.
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Azimi
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass.
authors.forename: Vemuri B
authors.initials: VB
authors.lastname: Reddy
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass; PUCRS, Programa de Pós-graduação em Biologia Celular e Molecular, Porto Alegre, Brazil.
authors.forename: Paula Juliana Seadi
authors.initials: PJS
authors.lastname: Pereira
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Talbot
authors.affiliation: FM Kirby Neurobiology Center, Children's Hospital Boston, Boston, Mass.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass. Electronic address: elerner@mgh.harvard.edu.
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Lerner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D008875:Middle Aged; D011537:Pruritus / Q000139:chemically induced / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018040:Receptors, Neurokinin-1 / Q000235:genetics; D011984:Sensory Receptor Cells / Q000187:drug effects; D013373:Substance P; D055815:Young Adult
chemical_list: D043562:Receptors, G-Protein-Coupled; D018040:Receptors, Neurokinin-1; D013373:Substance P; D002211:Capsaicin
keywords: Mas-related G protein–coupled receptors; Substance P; calcium imaging; dorsal root ganglion neurons; knockout mice; receptor antagonist