Playford R J, Marchbank T, Calnan D P, Calam J, Royston P, Batten J J, Hansen H F
Department of Medicine, Royal Postgraduate Medical School, London, England.
Gastroenterology. 1995 Jan;108(1):92-101. doi: 10.1016/0016-5085(95)90012-8.
BACKGROUND/AIMS: Epidermal growth factor (EGF) is present in gastric juice and has potent mitogenic properties. The stability of EGF in gastric juice under various physiological and pathophysiological conditions was examined.
Recombinant human EGF1-53 was incubated with HCl containing pepsin. We also determined the forms of EGF present in the gastric juice of patients under basal conditions, patients taking the acid suppressant omeprazole, patients with achlorhydria, and volunteers undergoing intragastric neutralization with NaHCO3 (n = 6 per group). Samples were analyzed using mass spectroscopy and/or high-pressure liquid chromatography followed by radioimmunoassay. The effect of acid and pepsin digestion on EGF bioactivity was determined using an in vitro hepatocyte bioassay and an in vivo cytoprotection assay in the rat stomach.
EGF1-53 was digested to the EGF1-49 and EGF1-46 forms in all samples containing pepsin when the pH was < 4. In gastric juice samples with pH > 4, the proportion of intact EGF increased to about 60%. For both methods of bioassay, intact EGF1-53 was about 3-4 times as potent as acid and pepsin-treated EGF.
EGF is produced in the 1-53 form but is rapidly cleaved to smaller, less active forms in acidic gastric juice. In contrast, only a small proportion of the EGF is cleaved if the pH is maintained above 4. This mechanism may be relevant to the healing process of acid suppressants.
背景/目的：表皮生长因子（EGF）存在于胃液中，具有强大的促有丝分裂特性。研究了EGF在各种生理和病理生理条件下在胃液中的稳定性。
将重组人EGF1-53与含胃蛋白酶的盐酸一起孵育。我们还测定了基础状态下患者、服用抑酸剂奥美拉唑的患者、无胃酸分泌的患者以及用碳酸氢钠进行胃内中和的志愿者（每组n = 6）胃液中EGF的存在形式。使用质谱和/或高压液相色谱，然后进行放射免疫测定对样品进行分析。使用体外肝细胞生物测定法和大鼠胃内细胞保护测定法确定酸和胃蛋白酶消化对EGF生物活性的影响。
当pH < 4时，在所有含胃蛋白酶的样品中，EGF1-53被消化为EGF1-49和EGF1-46形式。在pH > 4的胃液样品中，完整EGF的比例增加到约60%。对于两种生物测定方法，完整的EGF1-53的效力约为酸和胃蛋白酶处理的EGF的3-4倍。
EGF以1-53形式产生，但在酸性胃液中迅速裂解为较小的、活性较低的形式。相比之下，如果pH保持在4以上，只有一小部分EGF会被裂解。这种机制可能与抑酸剂的愈合过程有关。
