Gastrin-releasing peptide induces itch-related responses through mast cell degranulation in mice

Abstract

Gastrin-releasing peptide (GRP), secreted from the central terminals of primary afferents, is involved in the transmission of itch signals in the spinal dorsal horn. Although primary afferents containing GRP are distributed throughout the skin, the role of peripherally released GRP in the itch response is unknown. We investigated whether GRP acts on the skin to induce an itch response in mice. Intradermal injections of GRP18–27 (1–300nmol/site) elicited scratching. GRP18–27-induced scratching was inhibited by the μ-opioid receptor antagonist naltrexone hydrochloride, the BB2 bombesin receptor antagonist RC-3095, the H1 histamine receptor antagonists fexofenadine hydrochloride and chlorpheniramine maleate, and the PAR2 proteinase-activated receptor antagonist FSLLRY-NH2. Mast cell deficiency significantly, but not completely, reduced the GRP18–27-induced scratching. BB2 bombesin receptors are present in mast cells in the skin, and intradermal injection of GRP18–27, not only induced scratching, but also led to mast cell degranulation. GRP18–27-induced mast cell degranulation was inhibited by the BB2 bombesin receptor antagonist RC-3095. These results suggest that peripherally released GRP can induce an itch response, at least partly, through activation of BB2 receptors present in the mast cells, triggering their degradation and the release of histamine and the serine proteinase, tryptase.