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An increasing body of evidence has suggested trophic effects of peripheral nerves. In this study, the growth stimulatory properties of the sensory neuropeptides vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin generelated peptide (CGRP), and somatostatin (SOM) on cultured human keratinocytes were investigated. It was shown that VIP, in the presence of lethally treated 3T3 fibroblast feeder cells and epidermal growth factor (EGF), stimulated proliferation of keratinocytes in a dose-dependent manner, whereas SP, CGRP, and SOM were ineffective. VIP stimulated adenylate cyclase activity in membranes obtained from cultured keratinocytes in a dose-dependent manner, indicating an involvement of cAMP as second messenger in this reaction. Furthermore, 125I-labeled VIP was shown to bind to cultured keratinocytes and this binding could be displaced by addition of unlabeled VIP, suggesting the presence of specific receptors. It is therefore possible that VIP, released from sensory nerve endings in the skin, may act as a local mitogenic factor for human keratinocytes by stimulating adenylate cyclase activity via specific VIP receptors.

Vasoactive intestinal polypeptide stimulates cell proliferation and adenylate cyclase activity of cultured human keratinocytes.