Calcitonin gene-related peptide and prostaglandin E-2 but not substance P release induced by antidromic nerve stimulation from rat skin in vitro

The liberation of calcitonin gene-related peptide from rat skin in vitro in duced by antidromic electrical stimulation of unmyelinated units is demonst rated. Prostaglandin E-2 was released concomitantly during C-fiber stimulat ion. A dose-dependent increase in prostaglandin E-2 content of the eluate w as also observed in response to stimulation with substance P (10(-7) to 10( -5) M) and calcitonin gene-related peptide (10(-6) and 10(-5) M). In contra st, prostaglandin E-2 did not induce measurable release of neuropeptides. T he amount of calcitonin gene-related peptide released during suprathreshold electrical stimulation increased with pulse frequency. Calcitonin gene-rel ated peptide and prostaglandin release were completely inhibited in the pre sence of EMD 61753, a selective kappa-opioid receptor agonist. No significa nt release of substance P was observed. The data demonstrate a primary release of calcitonin gene-related peptide f rom unmyelinated but not myelinated primary afferents in the rat skin, whic h is accompanied by a secondary liberation of prostaglandin E-2, connecting neurogenic inflammation to general mechanisms of inflammation. (C) 1998 IB RO. Published by Elsevier Science Ltd.