Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 140, Issue 2, Pages 447-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.12.980
Keywords
Substance P; Mas-related G protein-coupled receptors; dorsal root ganglion neurons; calcium imaging; receptor antagonist; knockout mice
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Funding
- National Eczema Association
- Canadian Institute of Health and Research
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR057744, R21AR067399]
- National Institute of Child Health [HD018655]
- Human Development and National Institute of Neurological Disorders and Stroke [R37NS039518]
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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.
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