Ward J B, Sutton R, Jenkins S A, Petersen O H
Physiological Laboratory, University of Liverpool, England.
Gastroenterology. 1996 Aug;111(2):481-91. doi: 10.1053/gast.1996.v111.pm8690215.
BACKGROUND & AIMS: Disruption of pancreatic exocrine secretion is an important feature of acute pancreatitis. Because cytosolic calcium is a key intracellular messenger controlling pancreatic secretion, this study examined patterns of calcium signaling during the early stages of cerulein-induced pancreatitis.
Mice were administered hourly intraperitoneal injections of cerulein (50 micrograms/kg), and paired controls were administered saline. Acini were isolated by collagenase from pancreatic tissue harvested after injections 1, 3, 5, and 7 and were loaded with Fura-2. Individual cellular calcium responses to acetylcholine and cholecystokinin were studied using digital imaging.
The proportion of cells maintaining a normal oscillatory calcium response to physiological secretagogue stimulation diminished progressively after increasing cerulein injections. Also, the normal polarized spatial pattern of calcium Increase within individual acinar cells was progressively lost. A sustained response to high-dose stimulation was maintained but with diminishing amplitude. The characteristic calcium response to the Ca(2+)-adenosine triphosphatase inhibitor thapsigargin was maintained, implying that calcium reuptake and extrusion were not impaired.
Progressive disruption of physiological patterns of pancreatic acinar cell calcium signaling, notably in the secretory pole of the cell, is an early feature of pancreatitis induced by cerulein hyperstimulation. These changes may be important in contributing to the disruption of exocrine secretion in acute pancreatitis.
胰腺外分泌功能紊乱是急性胰腺炎的一个重要特征。由于胞质钙是控制胰腺分泌的关键细胞内信使，本研究检测了蛙皮素诱导的胰腺炎早期钙信号传导模式。
给小鼠每小时腹腔注射一次蛙皮素（50微克/千克），配对对照组注射生理盐水。在注射1、3、5和7小时后，从胰腺组织中用胶原酶分离出腺泡，并加载Fura-2。使用数字成像技术研究单个细胞对乙酰胆碱和胆囊收缩素的钙反应。
随着蛙皮素注射次数增加，对生理促分泌剂刺激保持正常振荡钙反应的细胞比例逐渐减少。此外，单个腺泡细胞内钙增加的正常极化空间模式也逐渐丧失。对高剂量刺激的持续反应得以维持，但幅度逐渐减小。对Ca(2+)-三磷酸腺苷酶抑制剂毒胡萝卜素的特征性钙反应得以维持，这意味着钙的再摄取和外排未受损。
胰腺腺泡细胞钙信号传导的生理模式逐渐紊乱，尤其是在细胞的分泌极，是蛙皮素过度刺激诱导的胰腺炎的早期特征。这些变化可能对急性胰腺炎外分泌功能紊乱起重要作用。
