Feurle G E, Hamscher G, Firat A E
DRK-Krankenhaus Neuwied, University of Bonn, Germany.
Pancreas. 1995 Apr;10(3):281-6. doi: 10.1097/00006676-199504000-00010.
The gastrointestinal peptide cholecystokinin (CCK) has been shown to stimulate pancreatic growth in the adolescent and adult rat. However, little is known about the role of gastrointestinal hormones in the regulation of organ formation during fetal development. We therefore examined the effects of the CCK receptor antagonist devazepide (25 micrograms/h) and an antigastrin/CCK monoclonal immunoglobulin G on the maternal and fetal rat pancreas. These substances were infused subcutaneously with minipumps in female rats during the entire period of gestation. At the end of gestation, the rats were killed and the pancreata of the dams and their litter were examined for DNA and protein. In the dams, the receptor antagonist and the antibody against CCK/gastrin had no effect. In the newborns, the CCK receptor antagonist led to a significant reduction of the protein and DNA concentration [protein in controls, 105.0 +/- 3.75 micrograms/mg pancreatic tissue; in the antagonist group, 91.9 +/- 4.2 micrograms/mg pancreatic tissue (p < 0.05); DNA in controls, 1.28 +/- 0.19 micrograms/mg pancreatic tissue; in the antagonist group, 0.48 +/- 0.06 micrograms/mg pancreatic tissue (p < 0.05) (mean +/- SEM)]. Immune neutralization of CCK/gastrin in the maternal-fetal circulation induced a reduction of the protein concentration in the fetal pancreas (85.3 +/- 3.06 micrograms/mg pancreatic tissue; p < 0.01) but had no effect on fetal pancreatic DNA. Additional experiments indicated effective concentrations of the CCK receptor antagonist in fetal pancreatic tissue and free binding sites of the circulating antibody. In conclusion, the study provides evidence that CCK and its analogues are involved in fetal pancreatic organogenesis.
胃肠肽胆囊收缩素（CCK）已被证明可刺激青春期和成年大鼠的胰腺生长。然而，关于胃肠激素在胎儿发育过程中器官形成调节中的作用知之甚少。因此，我们研究了CCK受体拮抗剂地伐西匹（25微克/小时）和抗胃泌素/CCK单克隆免疫球蛋白G对母鼠和胎鼠胰腺的影响。在整个妊娠期，通过微型泵将这些物质皮下注入雌性大鼠体内。妊娠末期，处死大鼠，检查母鼠及其幼崽的胰腺中的DNA和蛋白质。在母鼠中，受体拮抗剂和抗CCK/胃泌素抗体没有作用。在新生鼠中，CCK受体拮抗剂导致蛋白质和DNA浓度显著降低[对照组蛋白质含量为105.0±3.75微克/毫克胰腺组织；拮抗剂组为91.9±4.2微克/毫克胰腺组织（p<0.05）；对照组DNA含量为1.28±0.19微克/毫克胰腺组织；拮抗剂组为0.48±0.06微克/毫克胰腺组织（p<0.05）（平均值±标准误）]。母胎循环中CCK/胃泌素的免疫中和导致胎儿胰腺中蛋白质浓度降低（85.3±3.06微克/毫克胰腺组织；p<0.01），但对胎儿胰腺DNA没有影响。额外的实验表明胎儿胰腺组织中CCK受体拮抗剂的有效浓度以及循环抗体的游离结合位点。总之，该研究提供了证据表明CCK及其类似物参与胎儿胰腺器官发生。
