Concentration of Pancreozymin as a Determinant of the Exocrine-Endocrine Partition of Pancreatic Enzymes

Abstract

1. Recent evidence suggests that the pancreatic digestive enzymes are secreted not only into the digestive tract via the gland lumen (exocrine), but also into the blood stream (endocrine). This dual secretion has been designated the 'exocrine-endocrine partition' of enzymes and their precursors, and was investigated in both the isolated and perfused rat pancreas, and the rat pancreas in situ. 2. The release of amylase was accompanied by the release of precursors of proteolytic enzymes either into the common duct or into the portal vein, and it was measured as a representation of release of pancreatic enzymes. 3. When the isolated pancreas was perfused with Krebs-Henseleit solution containing pancreozymin 0.2 u./ml, the amylase output into the common duct was markedly increased, whereas the output into the vein was slightly increased. When the concentration of pancreozymin was increased up to 1.5 u./ml, the output into the vein was markedly increased in contrast to a small increase in the output into duct. 4. Corresponding with the increase in output into the vein, acinar cells exhibiting high effective membrane resistances increased in number during perfusion of pancreozymin at a high concentration. 5. Enhanced release due to pancreozymin into the vein and into the duct was negated when calcium was omitted from the perfusing medium. 6. As a high dose of pancreozymin was injected repeatedly into the rat in situ, the blood concentration of amylase became higher but the increase in the output into the common duct became lower. 7. It is concluded that pancreatic enzymes and precursors preserved in zymogen granules may be extruded into the acinar lumen by the common calcium-dependent cellular processes; then, some of the secretory products may leak into the portal vein via enlarged intercellular spaces when a high concentration of pancreozymin is present.

The electrogenic sodium pump in the hyperpolarizing and secretory effects of pancreozymin in the pancreatic acinar cell.

“…Relation between amylase output and concentration of Pz It has been shown that the secretary response varied markedly with the concentration of Pz used: higher concentrations of Pz increased amylase output into the portal vein in contrast to a small increase in the output into the common duct (Saito & Kanno, 1973), and the highest concentration produced a lower output (Debray, Vaille, De La Tour, Rose & Souchard, 1963; Leroi, Morisset & Webster, 1971;F6lsch & Wormsley, 1973; N. Ueda and T. Kanno, unpublished data). As a first approach to confirm the hyperpolarizing effect of Pz, an attempt was made to determine the concentration of Pz that produced the highest and most prolonged amylase output in the isolated and perfused rat pancreas.…”

Redistribution of amylase activity accompanying its secretion by the pancreas.

“…Regarding the former possibility, cholinergic stimulation and the peptide hormone cholecystokinin-pancreozymin can greatly augment the basolateral flux of amylase (7-10, 12, 13). This flux may be quite large and has been estimated to account for as much as 20% ofmaximal duct-directed secretion under certain circumstances (7,8,10,12,13 3-hr period and a proportional increase in degradative rate (10-fold), then there would also be a 10-fold increase in amylase activity in the gut. Thus, in order to explain the absence of such an increase in terms of degradation, degradation would have to have been enhanced to a substantially greater degree than secretion.…”

“…The first is that digestive enzymes can be reabsorbed intact although not necessarily in unaltered chemical form (1)(2)(3)(4)(5)(6) and that, at least after several hours of highly augmented secretion, enzyme appears to be conserved in this fashion (2). The second is that there is a substantial flux of at least some digestive enzymes from pancreas to blood-an endocrine secretion that can be greatly enhanced by natural secretagogues and that has been shown to be capable of rates as large as 10-20% of maximal duct-directed secretion (7)(8)(9)(10)(11)(12)(13).…”

Ultrastructure of Intercellular Junctions in the Rat Exocrine Pancreas Stimulated by Pancreozymin

“…The other five rats were perfused in the same way but adding pancreozymin (PZ, Eizai, Japan) to the perfusate in a concentration of 1.5 C.H.R.u/ml. Since it is reported that the activity of certain pancreatic enzymes in the portal vein reaches the maximum level when PZ is infused into the blood vessels of the rat in a concentration of 1.5 C.H.R.u/ml (SAITO and KANNO, 1973), this dose of PZ was used in the present study. Subsequently, each animal was again perfused with 70-80ml of paraformaldehyde/glutaraldehyde (PA/GA) fixative for 5-8min.…”

“…However, the transport mechanism and pathways of the enzymes from the acinar cell into the blood stream remain obscure. Of particular interest for morphologists is the report described by some physiologists (SAITO and KANNO, 1973), who suggested that the pancreatic enzymes are first secreted into the lumen from the apical cytoplasm of the acinar cells (PALADE, 1975), and then, take the passage into blood vessels by passing through the intercellular spaces between acinar cells when a high concentration of pancreozymin is present.…”