Histamine H-1 and H-2 receptor antagonists accelerate skin barrier repair and prevent epidermal hyperplasia induced by barrier disruption in a dry environment

Keratinocytes have histamine H-1 and H-2 receptors, but their functions are poorly understood. To clarify the role of histamine receptors in the epide rmis, we examined the effects of histamine receptor antagonists and agonist s applied epicutaneously on the recovery of skin barrier function disrupted by tape stripping in hairless mice. Histamine H-2 receptor antagonists fam otidine and cimetidine accelerated the recovery of skin barrier function, b ut histamine and histamine H-2 receptor agonist dimaprit delayed the barrie r repair. Application of compound 48/80, a histamine releaser, also delayed the recovery. Imidazole, an analog of histamine, had no effect. The histam ine H-1 receptor antagonists diphenhydramine and tripelennamine accelerated the recovery. Histamine H-3 receptor agonist N-alpha-methylhistamine and a ntagonist thioperamide had no effect. In addition, topical application of f amotidine or diphenhydramine prevented epidermal hyperplasia in mice with s kin barrier disrupted by acetone treatment in a dry environment (humidity < 10%) for 4 d. In conclusion, both the histamine H-1 and H-2 receptors in th e epidermis are involved in skin barrier function and the cutaneous conditi on of epidermal hyperplasia.