title: 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.
authors.affiliation: National Ageing Research Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Z
authors.initials: Z
authors.lastname: Khalil
authors.forename: S L
authors.initials: SL
authors.lastname: Townley
authors.forename: M A
authors.initials: MA
authors.lastname: Grimbaldeston
authors.forename: J J
authors.initials: JJ
authors.lastname: Finlay-Jones
authors.forename: P H
authors.initials: PH
authors.lastname: Hart
mesh_terms: D000818:Animals; D001768:Blister / Q000503:physiopathology; D015550:Cell Degranulation; D003877:Dermatitis, Contact / Q000503:physiopathology; D005260:Female; D006614:Hindlimb; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000187:drug effects; D009479:Neuropeptides / Q000172:deficiency / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012677:Sensation / Q000502:physiology*; D012867:Skin / Q000098:blood supply; D013237:Stereoisomerism; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology*
chemical_list: D009479:Neuropeptides; D014560:Urocanic Acid