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Perfusion of cis-urocanic
acid over peripheral sensory nerves stimulates neuropeptide release
Hart, Prue1,
Khalil, Zeinab2, Townley, Scott1,
Grimbaldeston, Michele1 and Finlay-Jones, John1
Dept Microbiology & ID, School of Medicine, Flinders University, Australia1
National Ageing Research Institute, University of Melbourne, Australia2
Abstract-
Previous studies using an antibody to cis-urocanic acid (cis-UCA)
and mast cell-depleted mice implicated both cis-UCA and mast
cells in the mechanisms by which UVB light suppresses systemic contact
hypersensitivity responses in mice. In the absence of a direct stimulatory
effect of cis-UCA 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-UCA on
cutaneous blood flow. Cis-UCA but not trans-UCA increased
microvascular flow by a mechanism largely dependent on the combined
activity of the neuropeptides, substance P and calcitonin gene-related
peptide (CGRP). Perfusion of cis-UCA over the base of blisters
induced in sensory neuropeptide-depleted rats did not have any stimulatory
effect above that seen with perfusion of cis-UCA together with
neuropeptide receptor antagonists in control rats. There was a small
direct effect of cis-UCA on microvascular blood flow. As both
substance P and CGRP could directly degranulate connective tissue mast
cells, this study suggests that cis-UCA indirectly activates
mast cells via its effects on peripheral terminals of unmyelinated primary
afferent sensory nerves. Cis-UCA-induced neuropeptides may also
contribute to UVB-induced cutaneous inflammation and alterations to
Langerhans cell activity.
Keywords: mast
cells, histamine, rodent
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