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评估钙在离体大鼠胰腺腺泡细胞毒性损伤中的作用。

Evaluation of the role of calcium in cytotoxic injury in isolated rat pancreatic acini.

作者信息

Majumdar A P, Vesenka G D, Dubick M A, Geokas M C

出版信息

Biochem Biophys Res Commun. 1986 Sep 14;139(2):530-7. doi: 10.1016/s0006-291x(86)80023-7.

DOI:10.1016/s0006-291x(86)80023-7
PMID:2429653
Abstract

The role of extracellular Ca2+ in pancreatic acinar membrane damage (cellular injury) by nicotine, membrane-active agents (mellitin, snake venom and Ca2+ ionophore A23187) and secretagogues (CCK-8 and secretin) was investigated. Freshly isolated dispersed pancreatic acini from 18 h fasted adult rats were incubated with one of the aforementioned agents, in the absence and presence of Ca2+. Cellular injury was assessed by measuring the release of pulse-labeled 51Cr and LDH. In addition, release of amylase, trypsinogen and chymotrypsinogen was also determined. In the absence of Ca2+ nicotine (6 mM) caused a profound release of 51Cr and LDH as well as amylase, trypsinogen and chymotrypsinogen from the isolated pancreatic acini. Release of these enzymes and 51Cr decreased sharply with addition of increasing concentrations (0.25-5 mM) of Ca2+. Release of 51Cr and amylase by snake venom (50 micrograms/ml) was found to be 100 and 25% higher, respectively, in the absence of Ca2+ than in its presence. On the other hand, the Ca2+ ionophore A23187 (7 micrograms/ml) was found to be effective in releasing 51Cr and amylase only in the presence of Ca2+. CCK-8, (0.25nM), secretin (1 microM) and mellitin (0.5 microgram/ml) although significantly stimulated amylase secretion (225-350%) in the presence of Ca2+, none of the agents induced 51Cr release from acini, either in the absence or in the presence of extracellular Ca2+. It is concluded that the extracellular Ca2+ plays no specific role in cytotoxic injury in isolated pancreatic acini.

摘要

研究了细胞外钙离子在尼古丁、膜活性剂(蜂毒素、蛇毒和钙离子载体A23187)以及促分泌剂(胆囊收缩素-8和促胰液素)导致胰腺腺泡膜损伤(细胞损伤)过程中的作用。将18小时禁食的成年大鼠新鲜分离的分散胰腺腺泡与上述试剂之一在有无钙离子的情况下进行孵育。通过测量脉冲标记的51Cr和乳酸脱氢酶(LDH)的释放来评估细胞损伤。此外,还测定了淀粉酶、胰蛋白酶原和糜蛋白酶原的释放。在无钙离子的情况下,尼古丁(6 mM)可导致分离的胰腺腺泡中51Cr、LDH以及淀粉酶、胰蛋白酶原和糜蛋白酶原大量释放。随着钙离子浓度(0.25 - 5 mM)的增加,这些酶和51Cr的释放量急剧下降。发现蛇毒(50微克/毫升)在无钙离子时释放51Cr和淀粉酶的量分别比有钙离子时高100%和25%。另一方面,发现钙离子载体A23187(7微克/毫升)仅在有钙离子存在时才有效释放51Cr和淀粉酶。胆囊收缩素-8(0.25 nM)、促胰液素(1 microM)和蜂毒素(0.5微克/毫升)虽然在有钙离子存在时能显著刺激淀粉酶分泌(225 - 350%),但在细胞外有无钙离子的情况下,这些试剂均未诱导腺泡释放51Cr。得出的结论是,细胞外钙离子在分离的胰腺腺泡的细胞毒性损伤中不发挥特定作用。

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