No abstract

Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini. Am. J. Physiol. 235(s): E517-E524, 1978 or Am. J. Physiol. Endocrinol. Metab. Gastrointest. Physiol. 4(5): E517-E524, 1978.-Isolated pancreatic acini were prepared by a new method from mouse and rat pancreases by digestion with purified collagenase and chymotrypsin followed by mechanical shearing. Acini were structurally similar to those of the intact pancreas, having a normal luminal structure but with the basal acinar cell membranes exposed to the incubation medium. Amylase release in response to both cholinergic analogues and the cholecystokinin analogues caerulein and pentagastrin was comparable to that of the intact pancreas, but was much greater than previously reported for isolated acinar cells. Cholinergic-stimulated release was inhibited by atropine with a Ki value of 1.4 nM which is comparable et al., (13) who further purified collagenase and then added back individual contaminants.

No abstract

Previous studies have suggested a role for glucocorticoids in the differentiation of the acinar pancreas. We have now used the rat tumor cell line AR42J, derived from the acinar pancreas, to directly study this effect of glucocorticoids in vitro. The steroid hormones dexamethasone, corticosterone, aldosterone, and progesterone, but not estrogen, increased both the amylase content and the number of secretory granules of these cells. The potencies of the steroids were directly related to their effectiveness as glucocorticoids; dexamethasone was the most potent hormone and gave maximal effects at 100 nM. Morphometric analyses revealed that dexamethasone increased the volume density of granules 5.5-fold from 0.20 + 0.08 to 1.10 + 0.20% (n = 4) of the cytoplasmic volume. Dexamethasone treatment also increased the volume density of rough endoplasmic reticulum 2.4-fold from 1.20 ___ 0.09 to 2.86 + 0.30% (n = 5) of the cytoplasmic volume. After 48 h of dexamethasone treatment the cellular content of amylase increase eightfold from 2.8 + 0.4 to 22.6 + 3.8 U/mg protein (n = 6). This effect of dexamethasone was discernible after 12 h of incubation and approached maximal stimulation after 72 h of incubation. The increases in cellular amylase content were due to increased amylase synthesis as shown by specific immunoprecipitation of [3SS]methionine-labeled proteins. Moreover, in vitro translation of cellular mRNA indicated that dexamethasone treatment increased amylase mRNA. Dexamethasone treatment also led to increased secretion of amylase in response to the secretagogue cholecystokinin. These data indicate, therefore, that glucocorticoids induce a more highly differentiated phenotype in AR42J pancreatic cells, and they suggest that glucocorticoids act via the enhanced transcription of specific mRNAs for acinar cell proteins.Steroid hormones exert many of their effects on target cells by modulating the expression of genes for specific proteins. Prior studies have suggested that glucocorticoids influence the morphological differentiation of the exocrine pancreas, and that they increase the expression of genes for amylase and possibly other digestive enzymes. In vivo, injections of glucocorticoids lead to increased amylase activity in the young rat (18) and the chick embryo (4). Also, adrenalectomy has been reported to decrease the pancreatic contents of amylase in the rat (8, 9). In vitro, glucocorticoids have been reported to enhance the accumulation of secretory enzymes in embryonic organ explants of the chicken (4) and the rat (11, 23-25, 29, 32). 1200To understand the direct interaction of glucocorticoids with the exocrine pancreas, the study of a cultured line of pancreatic acinar cells would be beneficial. Prior studies demonstrated the usefulness of a transplantable pancreatic acinar tumor in understanding normal pancreatic acinar physiology (13)(14)(15). In the present study, we used the AR42J cell line, which was derived from a chemically induced carcinoma of the acinar pancreas (16). These cells have been...

In the present study we used a bioassay system for measuring plasma cholecystokinin (CCK) to evaluate whether CCK has a physiologic role in regulating gastric emptying in humans. Plasma CCK levels and gastric emptying after ingestion of a mixed liquid meal were determined in five normal male volunteers. Fasting CCK levels averaged 0.8±0.1 pM and increased to 6.5±1.0 pM within 10 min of drinking the mixed meal. CCK levels remained elevated for up to 90 min. Gastric emptying after a meal was slow, at the end of the 90 min 68% of the original volume remained in the stomach. The rate of gastric emptying of water was then measured in the same individuals with a simultaneous infusion of either saline, or one of two doses of CCK (12 pmol/ kg per h and 24 pmol/kg per h). With the saline infusion, plasma CCK levels did not increase above basal and gastric contents emptied rapidly. At the end of 90 min only 7% of the original volume remained in the stomach. The lower dose of CCK resulted in a plasma level of 3.4 pM which both reproduced the average postprandial plasma level and caused a significant delay in gastric emptying. The higher dose of CCK achieved plasma levels of 8 pM and resulted in a delay in gastric emptying that was similar to that seen with the mixed meal. Since exogenous CCK at concentrations which occur postprandially delays gastric emptying, we conclude that CCK is a physiologic regulator of gastric emptying.