Selective exocytosis of zymogen granules induces non-parallel secretion in short-term cholecystokinin-stimulated rats

Abstract

Parallel studies on pancreatic enzyme secretion and zymogen granule enzyme composition have been carried out in rats subjected to infusion of cholecystokinin (CCK) (1·25 µg/kg per h) over 30 min. Flow cytometric analysis showed a significant decrease in the mean value of granule size after CCK stimulation. The amount of trypsinogen stored in each individual zymogen granule was significantly lower at 30 min of CCK infusion, but no variation in intragranular amylase content was observed. As a result, the amylase/trypsinogen ratio was significantly increased in the zymogen granules that remained in the pancreas of rats stimulated with CCK for 30 min. A significantly greater proportion of trypsin than amylase was secreted after 30 min CCK infusion. Our results support the existence of different types of granules loaded with different proportions of enzymes. We conclude that short-term CCK stimulation induces the selective release of large granules containing a high proportion of trypsinogen, which leads to a non-parallelism of enzyme secretion.

Circadian pancreatic enzyme pattern and relationship between secretory and motor activity in fasting humans

“…These findings question the concept of strictly parallel secretion of pancreatic enzymes in humans, although the mechanisms underlying differential release of individual enzymes remain largely unknown. Potential mechanisms include selective changes of enzyme synthesis, selective intracellular transport and storage (17,18,69), and selective exocytosis or chemical modification of individual enzymes (89). A recent report supports the existence of different types of granules loaded with different proportions of enzymes.…”

“…A recent report supports the existence of different types of granules loaded with different proportions of enzymes. Large granules containing a high proportion of trypsinogen and less amylase were selectively released in response to short-term cholecystokinin stimulation (18). Alternatively, differences in enzyme content among different compartments, i.e., peri-and teleinsular cells (52,76), and varying sensitivities of these compartments to stimulatory and inhibitory mediators (31) might explain nonparallel pancreatic enzyme secretion.…”

IP3 Receptor Type 2 Deficiency Is Associated with a Secretory Defect in the Pancreatic Acinar Cell and an Accumulation of Zymogen Granules

“…the peri-insular area [39]) or possibly even within individual cells. Upon stimulus-secretion coupling, there is also support for the differential release of contents [40]. Thus our results could indicate that IP3R-dependent mechanisms control the exocytosis of selective pools of ZGs that, for example, house relatively larger amounts of trypsinogen over amylase.…”

Compartmentalization of Pancreatic Secretory Zymogen Granules as Revealed by Low-Voltage Transmission Electron Microscopy

“…Indeed, Rothman as well as others have shown that secretion of pancreatic enzymes can occur in a non-parallel fashion, so that the nature of the pancreatic juice does not correspond to a homogeneous mixture of all pancreatic enzymes. Selective discharge of certain proteins does occur under particular conditions of stimulated secretion (Adelson and Rothman 1975;Rothman 1976Rothman , 1981Dagorn, 1978;Adelson and Miller 1985;Sommer et al 1985;Rothman et al, 1991;de Dios et al 1999). On the other hand, Anderson, Jena, and colleagues (Anderson 2004;Jena 2004Jena , 2009) have introduced the concept of a discharge mechanism different from the classical exocytotic event (in which the entire granule fuses in one single event with the plasma membrane).…”