title: Histamine released from epidermal keratinocytes plays a role in α-melanocyte-stimulating hormone-induced itching in mice.
abstract: Sunburn, wound repair, and chronic renal failure with hemodialysis are usually accompanied by both pigmentation and itching. Proopiomelanocortin-derived α-melanocyte-stimulating hormone (α-MSH) is produced in response to external stimuli, such as UV irradiation, and is involved in cutaneous pigmentation. However, it is unclear whether α-MSH is also involved in the itching. We therefore investigated whether α-MSH elicited itch-related responses in mice. We found that an intradermal injection of α-MSH induced hind-paw scratching, an itch-related response, in mice. The α-MSH-induced scratching was inhibited by the μ-opioid receptor antagonist naltrexone and the H1 histamine receptor antagonist terfenadine. In mast cell-deficient mice, α-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 α-MSH induced the release of histamine from Pam212 cells. These findings indicate that α-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 α-MSH-induced itching.
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshihisa
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address: shimizut@med.u-toyama.ac.jp.
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002460:Cell Line; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects*; D006640:Histidine Decarboxylase / Q000378:metabolism; D006728:Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D007271:Injections, Intradermal; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011537:Pruritus / Q000139:chemically induced; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects; D000521:alpha-MSH / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D006728:Hormones; D000521:alpha-MSH; D006632:Histamine; D006640:Histidine Decarboxylase