Neuropeptides and phorbolester-induced skin tumor promotion

我们研究了一些神经肽(NP)与皮肤中肿瘤促进过程的关系。使用的神经递质包括P物质(SP)、降钙素基因相关肽(CGRP)、血管活性肠肽(VIP)、神经生长因子(NGF)、β-内啡肽(β-EP)和生长抑素(SOM)。作为一种促进肿瘤的刺激。用12-o-十四烷基苯酚-13-乙酸酯(TPA)处理豚鼠皮肤，对组织或血中CGRP、VIP、NGF、SOM浓度无影响。TPA处理后6小时组织中SP浓度升高，12小时内血中SP浓度升高。下一步，研究了NPs和鸟氨酸脱羧酶(ODC)之间的相互关系，鸟氨酸脱羧酶是肿瘤促进过程的标志酶。NGF或β-EP对TPA诱导的ODC活性无影响。另一方面，SP、CGRP和SOM在TPA处理后3、6和9h对TPA诱导的ODC活性的抑制约为60%。VIP呈双相作用。VIP处理前刺激ODC活性，VIP处理后抑制ODC活性。任何NP对组织切片中ODC mRNA水平和TPA刺激的角质形成细胞增殖均无影响。这些结果提示TPA诱导的皮肤肿瘤促进过程与NPs之间存在相互作用。

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.