Studies on the pancreas of the guinea pig. Parallel processing and discharge of exocrine proteins.

The discharge and the intracellular transport of the exocrine proteins produced by the guinea pig pancreas have been investigated in the in vitro lobule system described by SCHEELE, G. A., AND PALADE, G. E. (1975) J. Biol. Chem. 250, 2660-2670. The inquiry was carried out on a protein-specific basis by using the sodium dodecyl sulfate polyacrylamide gel electrophoretic procedures worked out by TARTAKOFF, A. M., GREENE, L. J., AND PALADE, G. E. (1974) J. Biol; Chem. 249, 7420-7431. The results show that the same protein mixture is discharged by the lobules regardless of whether stimulation is by carbamylcholine (which mimics the action of acetylcholine), caerulein (which mimics the action of pancreozymin), or by 75 mM KCl. When no stimulant is present, the small quantity of discharged protein (resting secretion) also has the same composition. Analysis of successive secretion aliquots collected over a period of 2 hours of continuous timulation by carbamylcholine showed that the composition of the secretory output remains quasi-constant with time; therefore, the exocrine proteins appear to be discharged in parallel and in constant proportions, irrespective of stimulant and time under stimulation (for carbamylcholine). The analysis of a series of zymogen granule fractions prepared from lobules pulse-labeled with radioactive amino acids and chased for periods of 15 to 155 min shows that all major secretory proteins enter the condensing vacuoles of the Golgi complex and appear in zymogen granules in apparent synchrony.