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cis-Urocanic acid stimulates neuropeptide release from peripheral sensory nerves.

Abstract
Previous studies using an antibody to cis-urocanic acid and mast-cell-depleted mice implicated both cis-urocanic acid and mast cells in the mechanisms by which ultraviolet B light suppresses systemic contact hypersensitivity responses in mice. In the absence of a direct stimulatory effect of cis-urocanic acid on connective tissue mast cells, an indirect association was investigated. A blister induced in the rat hind footpad was used to examine the effects of slowly perfused cis-urocanic acid on cutaneous blood flow. cis-Urocanic acid but not trans-urocanic acid increased microvascular flow by a mechanism largely dependent on the combined activity of the neuropeptides, substance P and calcitonin gene-related peptide. Perfusion of cis-urocanic acid over the base of blisters induced in sensory-neuropeptide-depleted rats did not have any stimulatory effect above that seen with perfusion of cis-urocanic acid together with neuropeptide receptor antagonists in control rats. There was a small direct effect of cis-urocanic acid on microvascular blood flow. As both substance P and calcitonin gene-related peptide could directly degranulate connective tissue mast cells, this study suggests that cis-urocanic acid indirectly activates mast cells via its effects on peripheral terminals of unmyelinated primary afferent sensory nerves. cis-Urocanic-acid-induced neuropeptides may also contribute to ultraviolet-B-induced cutaneous inflammation and alterations to Langerhans cell activity.
AuthorsZ Khalil, S L Townley, M A Grimbaldeston, J J Finlay-Jones, P H Hart
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 117 Issue 4 Pg. 886-91 (Oct 2001) ISSN: 0022-202X [Print] United States
PMID11676828 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Neuropeptides
  • Urocanic Acid
Topics
  • Animals
  • Blister (physiopathology)
  • Cell Degranulation
  • Dermatitis, Contact (physiopathology)
  • Female
  • Hindlimb
  • Male
  • Mast Cells (drug effects, physiology)
  • Mice
  • Mice, Inbred BALB C
  • Microcirculation (drug effects)
  • Neuropeptides (deficiency, metabolism)
  • Peripheral Nerves (metabolism)
  • Peritoneal Cavity (cytology)
  • Rats
  • Rats, Sprague-Dawley
  • Sensation (physiology)
  • Skin (blood supply)
  • Stereoisomerism
  • Ultraviolet Rays
  • Urocanic Acid (pharmacology)

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