cis-urocanic acid stimulates neuropeptide release from peripheral sensory nerves

Previous studies using an antibody to cis-urocanic acid and mast-cell-deple ted 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-uro canic acid on connective tissue mast cells, an indirect association was inv estigated. A blister induced in the rat hind footpad was used to examine th e 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-urocani c acid over the base of blisters induced in sensory-neuropeptide-depleted r ats did not have any stimulatory effect above that seen with perfusion of c is-urocanic acid together with neuropeptide receptor antagonists in control rats. There was a small direct effect of cis-urocanic acid on microvascula r blood flow. As both substance P and calcitonin gene-related peptide could directly degranulate connective tissue mast cells, this study suggests tha t cis-urocanic acid indirectly activates mast cells via its effects on peri pheral terminals of unmyelinated primary afferent sensory nerves. cis-Uroca nic-acid-induced neuropeptides may also contribute to ultraviolet-B-induced cutaneous inflammation and alterations to Langerhans cell activity.