Pituitary adenylate cyclase activating polypeptide (PACAP) is localized inhuman dermal neurons and causes histamine release from skin mast cells

Objective and Design: Pituitary adenylate cyclase activating polypeptide (P ACAP) is a neuropeptide homologous with vasoactive intestinal polypeptide ( VIP) which is known to induce histamine release in human skin mast cells. P ACAP has not been detected in human skin. The purposes of the study were to investigate the occurrence of PACAP in human skin and to evaluate the hist amine releasing activity of the two common pro-PACAP products, PACAP-27 and PACAP-38. Material: Fourteen human surgical skin samples were obtained. PACAP and VIP were visualized by immunohistochemistry. A microdialysis technique was use d to measure histamine release in intact skin samples following intradermal injections of the peptides. Results: PACAP and VIP were localized in dermal nerves in connection with s weat glands. Intradermal injection of 3 or 10 mu m PACAP significantly rele ased histamine. Kinetics of histamine release showed peak release 2-4 min a fter skin challenge. Ten mu m of PACAP-27, VIP and somatostatin caused hist amine release with similar efficacy, whereas PACAP-38 was less effective. S ubstance P was twice as efficient as PACAP-27, whereas calcitonin gene-rela ted peptide did not release histamine. Conclusions: PACAP is found in human skin and is capable of releasing hista mine from skin mast cells.