title: Substance P and nitric oxide mediate would healing of ultraviolet photodamaged rat skin: evidence for an effect of nitric oxide on keratinocyte proliferation.
abstract: Since it has been demonstrated recently that neuropeptides are involved in wound healing in vivo we investigated the role of substance P (SP), calcitonin gene-related peptide (CGRP) and nitric oxide (NO) in regeneration of ultraviolet (UV) photodamaged rat skin by topical administration of specific antagonists. Topical application of the neurokinin (NK)1-receptor antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabi cyclo[ 2.2.2]octan-3-amine (CP-96,345) significantly delayed the reduction of the necrotic area at all timepoints post UV-irradiation, whereas topically administered NO synthase inhibitor NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) resulted in an increased necrotic area only at 7 days post-irradiation. More important, topically administered L-NAME but not SP reduced nuclear immunolabelling for proliferating cell nuclear antigen (PCNA) of the UV-exposed epidermis, suggesting a NO-mediated stimulation of keratinocyte proliferation. These findings suggest that endogenous SP and NO have a trophic function in wound healing after UV-induced damage of the skin which may be mediated by stimulation of angiogenesis or epidermal cell proliferation.
authors.affiliation: II. Physiologisches Institut der Universität Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Benrath
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.forename: F
authors.initials: F
authors.lastname: Gillardon
mesh_terms: D000818:Animals; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D013373:Substance P / Q000494:pharmacology*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D009569:Nitric Oxide; D013373:Substance P