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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:140

Article

Azimi, Ehsan^1,2  Reddy, Vemuri B.^1,2  Seadi Pereira, Paula Juliana^1,2,4  Talbot, Sebastien³  Woolf, Clifford J.³  Lerner, Ethan A.^1,2 

[1] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA USA

[2] Harvard Med Sch, Charlestown, MA USA

[3] Childrens Hosp Boston, FM Kirby Neurobiol Ctr, Boston, MA USA

[4] Pontificia Univ Catolica Rio Grande do Sul, Programa Posgrad Biol Celular & Mol, Porto Alegre, RS, Brazil

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

DOI  :  10.1016/j.jaci.2016.12.980

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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