Bilski J, Konturek P K, Krzyzek E, Konturek S J
Institute of Physiology, University School of Medicine, Kraków, Poland.
J Physiol Pharmacol. 1992 Sep;43(3):237-57.
Pancreatic secretion in rats is regulated by feedback inhibition of cholecystokinin (CCK) release by proteases in the gut lumen, but little is known about the role of gastric acid in this regulation. This study, carried out on conscious rats with large gastric fistulas (GF) and pancreatic fistulas, shows that diversion of pancreatic juice results in the progressive stimulation of pancreatic secretion only in rats with the GF closed. When the GF was kept open, the diversion resulted in only small increment in pancreatic secretion and this was accompanied by progressive increase in gastric acid outputs. Similar amounts of HCl instilled into the duodenum in rats with the GF open fully reproduced the increase in pancreatic secretion observed after the diversion of pancreatic juice. Pretreatment with omeprazole (15 mumol/kg) to suppress gastric acid secretion or with L-364,718 (5 mumol/kg) to antagonize CCK receptors in the diverted state, resulted in the decline in pancreatic secretion similar to that observed after opening the GF. CCK given s.c. (20-320 pmol/kg) failed to cause any significant rise in the post-diversion pancreatic secretion in rats with the GF closed, but stimulated this secretion dose-dependently when the GF was open. Camostate (6-200 mg/kg) in rats with pancreatic juice returned to the duodenum caused dose-dependent increase in pancreatic secretion, but after opening the GF or after omeprazole this increase was reduced by about 75%. This study provides evidence that gastric acid plays a crucial role in the pancreatic response to diversion of pancreatic juice or inhibition of luminal proteases, and that factors that eliminate gastric acid secretion reduce this response.
大鼠胰腺分泌受肠腔内蛋白酶对胆囊收缩素（CCK）释放的反馈抑制调节，但胃酸在这种调节中的作用却鲜为人知。本研究以患有大胃瘘（GF）和胰瘘的清醒大鼠为对象，结果显示，仅在GF闭合的大鼠中，胰液引流才会导致胰腺分泌逐渐受到刺激。当GF保持开放时，引流仅导致胰腺分泌少量增加，同时胃酸分泌量逐渐增加。向GF开放的大鼠十二指肠内注入等量的盐酸，完全重现了胰液引流后观察到的胰腺分泌增加情况。用奥美拉唑（15 μmol/kg）预处理以抑制胃酸分泌，或用L-364,718（5 μmol/kg）预处理以拮抗引流状态下的CCK受体，均可导致胰腺分泌下降，类似于打开GF后观察到的情况。皮下注射CCK（20 - 320 pmol/kg），在GF闭合的大鼠中未能使引流后胰腺分泌显著增加，但在GF开放时可剂量依赖性地刺激这种分泌。在胰液回流至十二指肠的大鼠中，卡莫司他（6 - 200 mg/kg）可导致胰腺分泌剂量依赖性增加，但在打开GF或使用奥美拉唑后，这种增加减少了约75%。本研究提供了证据表明，胃酸在胰腺对胰液引流或管腔蛋白酶抑制的反应中起关键作用，并且消除胃酸分泌的因素会降低这种反应。
