Herzig K H, Wilgus C, Schön I, Tatemoto K, Fölsch U R
Department of Internal Medicine, Christian-Albrechts-Universität, Kiel, Germany.
Regul Pept. 1998 Jun 30;74(2-3):193-8. doi: 10.1016/s0167-0115(98)00021-4.
Diazepam binding inhibitor (DBI1-86) has recently been isolated in search for a cholecystokinin (CCK)-releasing peptide in the duodenum that is responsible for the feedback regulation of exocrine pancreatic secretion. Synthetic porcine DBI1-86 stimulates CCK release in vivo and in vitro from isolated intestinal mucosal cells. We postulated that DBI intraduodenally releases CCK in a paracrine fashion and might be the missing link in the feedback regulation of exocrine pancreatic secretion. Somatostatin, peptide YY (PYY) and taurocholate are known to inhibit feedback-stimulated CCK release in the rat. In this study, we investigated the effect of somatostatin, PYY and taurocholate on DBI-stimulated CCK secretion. Dispersed rat intestinal mucosal cells were prepared from the proximal small bowel and continuously perfused. The perfusate was collected and the release of CCK into the medium was measured. DBI1-86 dose-dependently stimulated CCK release, with a maximal effect at 10(-9) M. Somatostatin blocked the DBI-stimulated CCK release. Pretreatment of the cells with pertussis toxin fully reversed the inhibitory effect of somatostatin on DBI-stimulated CCK secretion, suggesting that somatostatin exerts its action by an inhibitory G-protein. In contrast, PYY (10(-6) M) and taurocholate (10(-6) M) did not affect DBI stimulated CCK levels, indicating that they act through different mechanisms to inhibit feedback-stimulated CCK release.
地西泮结合抑制剂（DBI1 - 86）最近在十二指肠中被分离出来，用于寻找一种负责外分泌性胰腺分泌反馈调节的胆囊收缩素（CCK）释放肽。合成的猪DBI1 - 86在体内和体外均可刺激分离的肠黏膜细胞释放CCK。我们推测DBI以旁分泌方式在十二指肠内释放CCK，可能是外分泌性胰腺分泌反馈调节中缺失的环节。已知生长抑素、肽YY（PYY）和牛磺胆酸盐可抑制大鼠反馈刺激的CCK释放。在本研究中，我们研究了生长抑素、PYY和牛磺胆酸盐对DBI刺激的CCK分泌的影响。从近端小肠制备分散的大鼠肠黏膜细胞并进行连续灌注。收集灌注液并测量CCK释放到培养基中的量。DBI1 - 86以剂量依赖性方式刺激CCK释放，在10^(-9) M时达到最大效应。生长抑素可阻断DBI刺激的CCK释放。用百日咳毒素预处理细胞可完全逆转生长抑素对DBI刺激的CCK分泌的抑制作用，提示生长抑素通过抑制性G蛋白发挥作用。相比之下，PYY（10^(-6) M）和牛磺胆酸盐（10^(-6) M）不影响DBI刺激的CCK水平，表明它们通过不同机制抑制反馈刺激的CCK释放。
