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Publication : Histamine released from epidermal keratinocytes plays a role in α-melanocyte-stimulating hormone-induced itching in mice.

First Author  Shimizu K Year  2015
Journal  Am J Pathol Volume  185
Issue  11 Pages  3003-10
PubMed ID  26358220 Mgi Jnum  J:227010
Mgi Id  MGI:5699510 Doi  10.1016/j.ajpath.2015.07.015
Citation  Shimizu K, et al. (2015) Histamine Released from Epidermal Keratinocytes Plays a Role in alpha-Melanocyte-Stimulating Hormone-Induced Itching in Mice. Am J Pathol 185(11):3003-10
abstractText  Sunburn, wound repair, and chronic renal failure with hemodialysis are usually accompanied by both pigmentation and itching. Proopiomelanocortin-derived alpha-melanocyte-stimulating hormone (alpha-MSH) is produced in response to external stimuli, such as UV irradiation, and is involved in cutaneous pigmentation. However, it is unclear whether alpha-MSH is also involved in the itching. We therefore investigated whether alpha-MSH elicited itch-related responses in mice. We found that an intradermal injection of alpha-MSH induced hind-paw scratching, an itch-related response, in mice. The alpha-MSH-induced scratching was inhibited by the mu-opioid receptor antagonist naltrexone and the H1 histamine receptor antagonist terfenadine. In mast cell-deficient mice, alpha-MSH also elicited scratching, which was inhibited by terfenadine. The immunoreactivity for l-histidine decarboxylase, a key enzyme required for the production of histamine, histamine, and the melanocortin 1 and 5 receptors were shown in not only mast cells but also keratinocytes in murine skin. In addition to the expression of l-histidine decarboxylase and melanocortin 1 and 5 receptors, the mouse keratinocyte cell lines (Pam212) also showed immunoreactivity for l-histidine decarboxylase, histamine, and melanocortin 1 and 5 receptors. The application of alpha-MSH induced the release of histamine from Pam212 cells. These findings indicate that alpha-MSH may play an important role in the itching associated with pigmented cutaneous lesions and that the histamine released from keratinocytes is involved in this alpha-MSH-induced itching.
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