Nishi T, Hara H, Kasai T
Department of Bioscience and Chemistry, Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
Proc Soc Exp Biol Med. 1998 Sep;218(4):357-64. doi: 10.3181/00379727-218-44304.
Previously, we observed that pancreatic exocrine secretion was strongly enhanced after duodenal administration of guanidinated casein peptic hydrolysate (HGC) in rats with chronic bile-pancreatic juice (BPJ) diversion. Using a perifusion system of isolated dispersed rat intestinal mucosal cells, we investigated whether this phenomenon depends on a direct effect of protein on the intestine to release pancreatic secretagogues, such as cholecystokinin (CCK). Amylase release from isolated pancreatic acini was used as an assay to measure CCK or other pancreatic secretagogues in the effluents. Mucosal effluent with HGC stimulated amylase release from acini with or without soybean trypsin inhibitor (SBTI). Perifused effluent with low-concentrated SBTI did not stimulate amylase release. These results indicate that HGC stimulates release of pancreatic secretagogue from the intestinal mucosal cells independent of remaining trypsin activity in the isolated mucosa. Effluents with intact casein, its peptic digest, and homoarginine, which is a unique amino acid contained in HGC, were unable to stimulate amylase release from acini. Effluent with a high concentration of SBTI, which is rich in arginine residues, stimulated amylase release, but not with the same tryptic inhibitory effect of lima bean trypsin inhibitor, which is poor in arginine residues. These findings suggest that guanidyl residues in protein structure are responsible for release of pancreatic secretagogues from isolated intestinal mucosal cells. Finally, the increment of amylase release from pancreatic acini in response to the perifused effluent with HGC was eliminated in acini treated with a potent CCK antagonist, FK480. We conclude that in rats with BPJ diversion, HGC stimulates CCK release from the intestine by direct action on intestinal mucosa.
此前，我们观察到，在慢性胆汁胰液（BPJ）引流的大鼠中，十二指肠给予胍基化酪蛋白胃蛋白酶水解物（HGC）后，胰腺外分泌显著增强。我们使用分离的分散大鼠肠黏膜细胞灌注系统，研究了这种现象是否依赖于蛋白质对肠道的直接作用，以释放胆囊收缩素（CCK）等胰腺促分泌素。从分离的胰腺腺泡释放淀粉酶用作测定流出物中CCK或其他胰腺促分泌素的方法。含有HGC的黏膜流出物刺激有或没有大豆胰蛋白酶抑制剂（SBTI）的腺泡释放淀粉酶。含有低浓度SBTI的灌注流出物不刺激淀粉酶释放。这些结果表明，HGC刺激肠黏膜细胞释放胰腺促分泌素，与分离黏膜中剩余的胰蛋白酶活性无关。含有完整酪蛋白、其胃蛋白酶消化物和高精氨酸（HGC中含有的一种独特氨基酸）的流出物不能刺激腺泡释放淀粉酶。含有高浓度SBTI（富含精氨酸残基）的流出物刺激淀粉酶释放，但富含精氨酸残基的利马豆胰蛋白酶抑制剂没有相同的胰蛋白酶抑制作用时则不能刺激。这些发现表明，蛋白质结构中的胍基残基负责从分离的肠黏膜细胞释放胰腺促分泌素。最后，在用强效CCK拮抗剂FK480处理的腺泡中，对含有HGC的灌注流出物作出反应的胰腺腺泡淀粉酶释放增量被消除。我们得出结论，在BPJ引流的大鼠中，HGC通过直接作用于肠黏膜刺激CCK从肠道释放。
