DISASSEMBLY OF RAT PANCREATIC ACINAR CELL CYTOSKELETON DURING SUPRAMAXIMAL SECRETAGOGUE STIMULATION
DISASSEMBLY OF RAT PANCREATIC ACINAR CELL CYTOSKELETON DURING SUPRAMAXIMAL SECRETAGOGUE STIMULATION
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DOI：
10.1152/ajpgi.1995.268.2.g328
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发表时间：
1995-02-01
影响因子：
4.5
通讯作者：
ADLER, G
中科院分区：
文献类型：
--
作者：
JUNGERMANN, J;LERCH, MM;ADLER, G
在体内用超过最大刺激量的促分泌剂浓度刺激外分泌胰腺，会引起消化酶原在细胞内的分离、运输和胞吐功能的显著障碍。在生理条件下，细胞骨架的元素，尤其是微管和微丝，参与了这些细胞内事件的调节。我们给大鼠静脉注射超最大剂量(10微克·公斤(-1)·小时(-1)，长达6小时)，这是一种胆囊素的多肽类似物雨蛙素。为了研究免疫金标记腺泡细胞微丝和微管的超微结构变化，我们使用了针对肌动蛋白和β-微管蛋白的单抗。早在促分泌剂输注30分钟后，我们就发现外分泌细胞中的微管和微丝逐渐解体。在免疫印迹研究中，细胞骨架的这种分解伴随着其结构蛋白肌动蛋白和β-微管蛋白的降解。我们的结果表明，在胰腺超最大促分泌剂刺激时，最早的形态事件涉及微管和微丝的分解和降解。这一细胞生物学现象为消化酶的分离、运输和胞吐的紊乱提供了解释，这些酶被认为与胰腺的超最大刺激和胰腺炎的实验模型有关。
In vivo stimulation of the exocrine pancreas with concentrations of secretagogue in excess of a maximally stimulating dose causes a marked disturbance of the intracellular segregation, transport, and exocytosis of digestive enzyme zymogens. Under physiological conditions elements of the cytoskeleton, most notably microtubules and microfilaments, are involved in the regulation of these intracellular events. We infused caerulein, a peptide analogue of cholecystokinin, at a supramaximal dose (10 mu g.kg(-1).h(-1) for up to 6 h) intravenously in rats. To study the ultrastructural alterations of acinar cell microfilaments and microtubules by immunogold labeling, we used monoclonal antibodies directed against actin and beta-tubulin. As early as 30 min after the start of the secretagogue infusion we found a progressive disassembly of microtubules and microfilaments in exocrine cells. In immunoblot studies this disassembly of the cytoskeleton was paralleled by a degradation of its structural proteins actin and beta-tubulin. Our results indicate that the earliest morphological events during supramaximal secretagogue stimulation of the pancreas involve the disassembly and degradation of microtubules and microfilaments. This cell biological phenomenon offers an explanation for the disturbances of segregation, transport, and exocytosis of digestive enzymes, which are known to be associated with supramaximal stimulation of the pancreas and experimental models of pancreatitis.