Acceleration of asynchronous enzyme transport in the rat exocrine pancreas following hormonal stimulation in vivo.

We have measured the rate of secretion in vitro of individual rat exocrine pancreatic enzymes and proenzymes from cells in pancreatic lobules of control animals and animals subjected to 24 h optimal hormonal prestimulation with cerulein, in vivo. With the controls secreted proteins were first detectable at 20 to 25 min of chase after a 5-min pulse label, and the amount of total secretion increased slowly thereafter. With stimulated lobules secretion was first detectable at 10 to 15 min postpulse. Comparison of the rates of secretion from control and experimental lobules showed that 24 h prestimulation in vivo resulted in a fivefold increase in the rate of secretion. Measurement of the rates of secretion of the individual enzymes and proenzymes showed that they were all increased to the same extent. In both situations the serine endoproteases, proelastase 2, chymotrypsinogen 1, and trypsinogen 1 and 2, were the most rapidly secreted proteins, while amylase, the procarboxypeptidases and prophospholipase A2 were amongst the slowest. The difference in the rates of secretion of proelastase 2 and prophospholipase A2, the two extremes, was three-fold before and after prestimulation, and their halftimes of secretion from the hormonally prestimulated lobules were 34 min and 190 min, respectively. Both electron microscopic autoradiography and immunocytochemistry showed that in the hormonally prestimulated cells the secreted proenzymes and enzymes followed the normal regulated exocytotic pathway and were transported between the Golgi apparatus and the apical plasma membrane in dense cored secretory granules.