Joshi V, Ray G S, Goldenring J R
Augusta Veterans Affairs Medical Center, Georgia, USA.
Dig Dis Sci. 1997 Jun;42(6):1194-8. doi: 10.1023/a:1018845805806.
Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) inhibit gastric acid secretion both in vivo and in vitro. Previous studies have indicated that EGF and TGF-alpha bind to the same EGF/TGF-alpha receptor. Nevertheless, we and others have previously demonstrated that inhibition of acid secretion by these growth factors requires concentrations of the peptides that are 10-fold higher than those necessary for induction of mitogenesis. Therefore, we have sought to investigate whether gastric parietal cells may possess a second EGF/TGF-alpha receptor class. Two systems were studied: First, [125I]TGF-alpha was cross-linked to the receptor in isolated rabbit parietal cell membranes, and labeled species were resolved on SDS-PAGE. Second, acid secretion was evaluated in pylorus-ligated waved-2 mutant mice, which carry a disabling point mutation in their classical EGF/TGF-alpha receptor. In isolated parietal cells, [125I]TGF-alpha was cross-linked into a single species of 170 kDa. Cross-linking was inhibited in the presence of unlabeled TGF-alpha with an IC50 of 80 nM. In the pylorus-ligated mice, control littermate mice demonstrated a dose-dependent inhibition of acid secretion by EGF with an IC50 of 20 micrograms/kg. In contrast, EGF had no inhibitory effect on acid secretion in waved-2 mice at concentrations up to 100 micrograms/kg. No alterations in parietal cell or gastrin cell numbers were observed. These results in both isolated rabbit parietal cells and waved-2 mice support the existence of only a single class of EGF/TGF-alpha receptors in parietal cells. Differences in growth factor affinity are likely due to the modification of the receptor or one of its coordinate regulators.
表皮生长因子（EGF）和转化生长因子-α（TGF-α）在体内和体外均能抑制胃酸分泌。以往的研究表明，EGF和TGF-α与同一种EGF/TGF-α受体结合。然而，我们和其他人之前已经证明，这些生长因子抑制胃酸分泌所需的肽浓度比诱导有丝分裂所需的浓度高10倍。因此，我们试图研究胃壁细胞是否可能存在第二类EGF/TGF-α受体。我们研究了两个系统：第一，将[125I]TGF-α与分离的兔壁细胞膜上的受体进行交联，并在SDS-PAGE上分离标记的物种。第二，在幽门结扎的waved-2突变小鼠中评估胃酸分泌，这些小鼠在其经典的EGF/TGF-α受体中携带一个致病变异点突变。在分离的壁细胞中，[125I]TGF-α被交联成一种170 kDa的单一物种。在未标记的TGF-α存在下，交联受到抑制，IC50为80 nM。在幽门结扎的小鼠中，对照同窝小鼠显示EGF对胃酸分泌有剂量依赖性抑制作用，IC50为20微克/千克。相比之下，在浓度高达100微克/千克时，EGF对waved-2小鼠的胃酸分泌没有抑制作用。未观察到壁细胞或胃泌素细胞数量的改变。在分离的兔壁细胞和waved-2小鼠中的这些结果支持壁细胞中仅存在一类EGF/TGF-α受体。生长因子亲和力的差异可能是由于受体或其协同调节因子之一的修饰。
