NEUROPEPTIDE-INDUCED AND CAPSAICIN-INDUCED HISTAMINE-RELEASE IN SKIN MONITORED WITH THE MICRODIALYSIS TECHNIQUE

Mast cells are thought to be involved in neurogenic inflammation in sk in, and numerous neuropeptides are known to degranulate mast cells, We monitored histamine release in skin in situ with the microdialysis me thod after skin challenge with neuropeptide injections (10 mu M substa nce P, vasoactive intestinal peptide and calcitonin gene-related pepti de), capsaicin injection (30 mu M) and 0.1% capsaicin cream with a moi st compress. Fractions were collected for 15 min each at 3.0 mu l/min. One hour after insertion of the probe, the baseline histamine level w as 4.5 +/- 4.5 nM (mean +/- SD, a = 20). Substance P (250 pmol) induce d histamine release peak (66.1 +/- 52.5 nM, n=8) in the 0-15 or 15-30 min fraction, Thereafter, the histamine concentration declined steadil y and rapidly and no second rise was observed, A single substance P in jection was sufficient to induce major histamine release in three out of four experiments; and the release kinetics of the second injection (Ih later) mimicked that of the first injection. Vasoactive intestinal peptide (100 and 250 pmol) induced a rapid release of histamine in 4 subjects comparable to substance P, whereas calcitonin gene-related pe ptide (250 pmol) did not release detectable amounts of histamine in 2 subjects tested. Capsaicin induced a low and rather non-significant re lease of histamine in 4 out of 5 patients who received capsaicin injec tion and in 2 out of 5 who were treated with capsaicin cream, The pres ent study shows that neuropeptides substance P and vasoactive intestin al peptide, but not calcitonin gene-related peptide, can induce activa tion of mast cells and release of histamine into the extracellular spa ce. The low release of histamine by capsaicin suggests low levels of n europeptides or infrequent morphological contacts between mast cells a nd sensory nerves in normal human skin, The microdialysis method can b e used for studying skin inflammatory reactions involving mast cells.