Substance P and nitric oxide mediate would healing of ultraviolet photodamaged rat skin: evidence for an effect of nitric oxide on keratinocyte proliferation.
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.
Benrath
J
J
II. Physiologisches Institut der Universität Heidelberg, Germany.
Zimmermann
M
M
Gillardon
F
F
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
D009569:Nitric Oxide; D013373:Substance P