A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat pancreatic secretion.
A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat pancreatic secretion.
复制标题
胆囊收缩素释放因子介导乙醇诱导的大鼠胰腺分泌刺激。
DOI：
10.1172/jci119186
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Steer,ML
中科院分区：
文献类型：
--
作者：
Saluja,AK;Lu,L;Yamaguchi,Y;Hofbauer,B;Rünzi,M;Dawra,R;Bhatia,M;Steer,ML
短期给药乙醇改变胰腺外分泌功能的机制尚不清楚。我们评估了乙醇给药对胰腺消化酶分泌的影响。在我们的研究中，麻醉和清醒的大鼠以足够的速度给予乙醇，使血液中乙醇浓度达到与临床中毒相关的水平。在血液乙醇水平稳定升高的2小时内，给予乙醇。我们报告静脉注射乙醇导致胰淀粉酶输出和血浆胆囊收缩素（CCK）水平的短暂增加。CCK-A受体拮抗剂L-364,718可完全抑制乙醇诱导的淀粉酶输出量的增加，而毒蕈碱胆碱能拮抗剂阿托品可部分抑制乙醇诱导的淀粉酶输出量的增加。通过在十二指肠内灌注胰蛋白酶或在给药期间用生理盐水灌胃十二指肠，可以完全阻止乙醇引起的淀粉酶输出量的增加。此外，一种cck释放因子的十二指肠内活性通过输注乙醇而增加。这些研究表明，给药乙醇引起大鼠胰腺外分泌增加。这种现象是由存在于十二指肠管腔内的胰蛋白酶敏感的cck释放因子介导的。这些观察结果使我们推测，cck介导的乙醇诱导的胰腺消化酶分泌的重复刺激可能在乙醇滥用与胰腺损伤发展相关的事件中发挥作用。
The mechanisms by which short-term ethanol administration alters pancreatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. In our studies, anesthetized as well as conscious rats were given ethanol at a rate sufficient to cause the blood ethanol concentration to reach levels associated with clinical intoxication. Ethanol was administered over a 2-h period during which blood ethanol levels remained stably elevated. We report that intravenous administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. The ethanol-induced increase in amylase output can be completely inhibited by the CCK-A receptor antagonist L-364,718 and partially inhibited by the muscarinic cholinergic antagonist atropine. The ethanol-induced rise in amylase output can be completely prevented by instillation of trypsin into the duodenum or by lavage of the duodenum with saline during ethanol administration. Furthermore, the intraduodenal activity of a CCK-releasing factor is increased by infusion of ethanol. These studies indicate that administration of ethanol causes rat pancreatic exocrine secretion to increase. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor which is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events which link ethanol abuse to the development of pancreatic injury.