DISASSEMBLY OF RAT PANCREATIC ACINAR CELL CYTOSKELETON DURING SUPRAMAXIMAL SECRETAGOGUE STIMULATION

In vivo stimulation of the exocrine pancreas with concentrations of se cretagogue in excess of a maximally stimulating dose causes a marked d isturbance of the intracellular segregation, transport, and exocytosis of digestive enzyme zymogens. Under physiological conditions elements of the cytoskeleton, most notably microtubules and microfilaments, ar e involved in the regulation of these intracellular events. We infused caerulein, a peptide analogue of cholecystokinin, at a supramaximal d ose (10 mu g.kg(-1).h(-1) for up to 6 h) intravenously in rats. To stu dy the ultrastructural alterations of acinar cell microfilaments and m icrotubules by immunogold labeling, we used monoclonal antibodies dire cted against actin and beta-tubulin. As early as 30 min after the star t of the secretagogue infusion we found a progressive disassembly of m icrotubules and microfilaments in exocrine cells. In immunoblot studie s this disassembly of the cytoskeleton was paralleled by a degradation of its structural proteins actin and beta-tubulin. Our results indica te that the earliest morphological events during supramaximal secretag ogue stimulation of the pancreas involve the disassembly and degradati on 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.