TY - JOUR
T1 - Gastrin-releasing peptide induces itch-related responses through mast cell degranulation in mice
AU - Andoh, Tsugunobu
AU - Kuwazono, Takashi
AU - Lee, Jung Bum
AU - Kuraishi, Yasushi
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Young Scientists (B) (# 22790063 ) and for Scientific Research (B) # 23390153 from the Ministry of Education, Culture, Sports, Science and Technology , Japan ( 22790063 ) and by Grants for Health Science from the Health, Labor and Welfare Ministry , Japan.
PY - 2011/10
Y1 - 2011/10
N2 - 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 GRP 18-27 (1-300 nmol/site) elicited scratching. GRP 18-27-induced scratching was inhibited by the μ-opioid receptor antagonist naltrexone hydrochloride, the BB 2 bombesin receptor antagonist RC-3095, the H 1 histamine receptor antagonists fexofenadine hydrochloride and chlorpheniramine maleate, and the PAR 2 proteinase-activated receptor antagonist FSLLRY-NH 2. Mast cell deficiency significantly, but not completely, reduced the GRP 18-27-induced scratching. BB 2 bombesin receptors are present in mast cells in the skin, and intradermal injection of GRP 18-27, not only induced scratching, but also led to mast cell degranulation. GRP 18-27-induced mast cell degranulation was inhibited by the BB 2 bombesin receptor antagonist RC-3095. These results suggest that peripherally released GRP can induce an itch response, at least partly, through activation of BB 2 receptors present in the mast cells, triggering their degradation and the release of histamine and the serine proteinase, tryptase.
AB - 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 GRP 18-27 (1-300 nmol/site) elicited scratching. GRP 18-27-induced scratching was inhibited by the μ-opioid receptor antagonist naltrexone hydrochloride, the BB 2 bombesin receptor antagonist RC-3095, the H 1 histamine receptor antagonists fexofenadine hydrochloride and chlorpheniramine maleate, and the PAR 2 proteinase-activated receptor antagonist FSLLRY-NH 2. Mast cell deficiency significantly, but not completely, reduced the GRP 18-27-induced scratching. BB 2 bombesin receptors are present in mast cells in the skin, and intradermal injection of GRP 18-27, not only induced scratching, but also led to mast cell degranulation. GRP 18-27-induced mast cell degranulation was inhibited by the BB 2 bombesin receptor antagonist RC-3095. These results suggest that peripherally released GRP can induce an itch response, at least partly, through activation of BB 2 receptors present in the mast cells, triggering their degradation and the release of histamine and the serine proteinase, tryptase.
KW - BB bombesin receptor
KW - GRP
KW - Itch, Gastrin-releasing peptide
KW - Mast cell
KW - Scratching
UR - http://www.scopus.com/inward/record.url?scp=80054060012&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2011.09.003
DO - 10.1016/j.peptides.2011.09.003
M3 - 学術論文
C2 - 21933692
AN - SCOPUS:80054060012
SN - 0196-9781
VL - 32
SP - 2098
EP - 2103
JO - Peptides
JF - Peptides
IS - 10
ER -