Reid T W, Murphy C J, Iwahashi C K, Foster B A, Mannis M J
Department of Ophthalmology and Visual Science, Texas Tech University Health Science Center, Lubbock 79430.
J Cell Biochem. 1993 Aug;52(4):476-85. doi: 10.1002/jcb.240520411.
The neuropeptide substance P (SP) was found to stimulate DNA synthesis and cell growth for epithelial cells (cornea and lens) in a serum-free environment. The length of treatment time was shown to be important since longer times shifted the dose-response curve to the left. In short-term DNA synthesis studies (40 h) the stimulation with SP (or synergism with insulin) was not apparent until close to 10 microM, however, when DNA synthesis assays were carried out over a long period of time (5 days) stimulation with SP was seen at 1 pM. The stimulation of DNA synthesis by SP was synergistic with insulin for lens epithelial cells, but little synergism was seen with corneal epithelial cells. It cell growth studies on lens epithelial cells SP also showed growth stimulation by itself and synergism with insulin at concentrations of 1-2 pM. The neuropeptide calcitonin gene related peptide (CGRP) showed no DNA synthesis stimulating ability on epithelial cells by itself at concentrations as high as 2.5 microM; however, it was synergistic with SP at a concentration of 0.025 microM. SP pretreatment of epithelial cells for 2 h causes an increase in cellular sensitivity to subsequent addition of either SP or insulin. This increase is consistent with the hypothesis that either the signal from SP persists after its removal from the cell or the dissociation time for SP from its receptor is longer than the wash time.
人们发现神经肽P物质（SP）在无血清环境中可刺激上皮细胞（角膜和晶状体）的DNA合成及细胞生长。结果表明治疗时间长短很重要，因为较长时间会使剂量反应曲线左移。在短期DNA合成研究（40小时）中，直到接近10微摩尔时，SP（或与胰岛素协同作用）的刺激作用才明显，然而，当长时间（5天）进行DNA合成检测时，在1皮摩尔时就能观察到SP的刺激作用。SP对晶状体上皮细胞的DNA合成刺激作用与胰岛素具有协同性，但对角膜上皮细胞几乎没有协同作用。在晶状体上皮细胞的细胞生长研究中，SP自身也显示出促生长作用，并且在1 - 2皮摩尔浓度下与胰岛素具有协同性。神经肽降钙素基因相关肽（CGRP）在高达2.5微摩尔的浓度下，自身对上皮细胞没有DNA合成刺激能力；然而，它在0.025微摩尔浓度下与SP具有协同性。上皮细胞用SP预处理2小时会导致细胞对随后添加的SP或胰岛素的敏感性增加。这种增加与以下假设一致，即要么SP的信号在从细胞中去除后仍然存在，要么SP从其受体上解离的时间长于冲洗时间。
