Ruellan C, Scemama J L, Clerc P, Fagot-Revurat P, Clemente F, Ribet A
Peptides. 1986;7 Suppl 1:267-71. doi: 10.1016/0196-9781(86)90200-7.
VIP and secretin control the secretory function of the normal pancreas. We analysed their regulatory functions in a human pancreatic cancer cell line: Capan-1. Saturation binding experiments with 125I-VIP showed the existence of one class of binding sites of very high affinity: KD 6.4 +/- 3.0 X 10(-11) M and a low Bmax: 12 fmoles/10(6) cells, in both intact cells and membrane preparations. This site has not yet been described in normal or tumorous digestive cells. Competition binding experiments let us characterize two more binding sites, KD: 2.1 +/- 0.7 X 10(-9) M and 5.0 +/- 0.6 X 10(-8) M and the corresponding Bmax: 120 and 500 fmoles/10(6) cells. These sites are similar to those found on cells of the digestive tract. Competition binding experiments gave the following IC50: 3.0 +/- 0.9 X 10(-9) M for VIP; 2 +/- 0.6 X 10(-6) M for PHI; and 1 +/- 0.7 X 10(-5) M for secretin. VIP elicited a cAMP rise, the half maximal response being obtained at 1.2 X 10(-10) M. Secretin induced a cAMP response but only for concentrations higher than 10(-8) M. VIP receptors were found to be modulated by two factors: cell ageing and cell density. Cells chronically treated with VIP showed a slight decrease of their proliferation; insulin exerted an opposite effect. It is concluded that at the difference of normal pancreatic cells, the present cell line lacks secretin-preferring receptors and acquires some of the properties of intestinal cells.
血管活性肠肽（VIP）和促胰液素控制着正常胰腺的分泌功能。我们分析了它们在人胰腺癌细胞系Capan-1中的调节功能。用125I-VIP进行的饱和结合实验表明，在完整细胞和膜制剂中均存在一类高亲和力的结合位点：解离常数（KD）为6.4±3.0×10⁻¹¹ M，最大结合容量（Bmax）较低，为12 fmol/10⁶个细胞。这种位点在正常或肿瘤性消化细胞中尚未见报道。竞争结合实验使我们鉴定出另外两个结合位点，KD分别为2.1±0.7×10⁻⁹ M和5.0±0.6×10⁻⁸ M，相应的Bmax分别为120和500 fmol/10⁶个细胞。这些位点与在消化道细胞中发现的位点相似。竞争结合实验得出以下半数抑制浓度（IC50）：VIP为3.0±0.9×10⁻⁹ M；胰高血糖素样肽（PHI）为2±0.6×10⁻⁶ M；促胰液素为1±0.7×10⁻⁵ M。VIP引起细胞内环磷酸腺苷（cAMP）升高，在1.2×10⁻¹⁰ M时达到半数最大反应。促胰液素诱导cAMP反应，但仅在浓度高于10⁻⁸ M时出现。发现VIP受体受两个因素调节：细胞老化和细胞密度。长期用VIP处理的细胞其增殖略有下降；胰岛素则发挥相反的作用。结论是，与正常胰腺细胞不同，该细胞系缺乏促胰液素偏好性受体，并获得了一些肠细胞的特性。
