Neuropeptides and phorbolester-induced skin tumor promotion

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We investigated relations of some neuropeptides (NP) and tumor promotion process in the skin. NPs used were substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), nerve growth factor (NGF), beta-endorphine (beta-EP) and somatostatin (SOM). As a tumor promotional stimulation. 12-o-tetradecanoypholbol-13-acetate (TPA) was applied to the guinea pig skin.TPA treatment had no effect on tissue or blood concentration of CGRP,VIP,NGF,SOM.SP concentation increased in the tissue in 6 hr after TPA treatment, and in the blood within 12 hr. beta-EP concentration increased only in the blood in 6 hr.As a next step, interrelations between NPs and ornithine decarboxylase (ODC), a marker enzyme for tumor promotion process, were investigated. NGF or beta-EP had no effect on TPA-induced ODC activity. On the other hand, SP,CGRP and SOM suppressed TPA-induced ODC activity by about 60% at 3,6 and 9 hrs after TPA treatment. VIP showed biphasic action. VIP pre-treatment stimulated ODC activity, but VIP post-treatment suppressed ODC activity. Any NP had no effect on ODC mRNA level and TPA-stimulated keratinocyte proliferation in tissue section.These results suggest interactions between TPA-induced tumor promotional process in the skin and NPs.