Nonparallel secretion of GP-2 from exocrine pancreas implies luminal coupling between acinar and duct cells

1994 ◽  
Vol 267 (1) ◽  
pp. G40-G51 ◽  
Author(s):  
S. D. Freedman ◽  
K. Sakamoto ◽  
G. A. Scheele
Keyword(s):  
Exocrine Pancreas ◽  
Acinar Cells ◽  
Zymogen Granule ◽  
Zymogen Granules ◽  
Pancreatic Acini ◽  
Glycosyl Phosphatidylinositol ◽  
Cellular Processes ◽  
Rat Exocrine Pancreas

The in vivo and in vitro secretion of glycoprotein-2 (GP-2), a glycosyl phosphatidylinositol (GPI)-anchored protein from the rat exocrine pancreas, was characterized. GP-2 was secreted in a nonparallel manner compared with amylase, a marker of secretory enzymes. Attenuated GP-2 secretion correlated with hormones that stimulated exocytosis in acinar cells. Augmented GP-2 secretion correlated with hormones that stimulated fluid and bicarbonate secretion from ductal elements. Immunofluorescence studies identified an enriched pool of GP-2 tightly bound to the apical membranes of acinar cells in addition to zymogen granules. This non-zymogen granule pool appears to represent the source of GP-2 released from acinar cells in a nonparallel manner. With the use of dispersed pancreatic acini largely devoid of ductal elements, GP-2 release was found to be augmented by alkaline pH. Thus GP-2 secretion appears to be modulated by two discrete cellular processes: 1) delivery of prereleased GP-2 within zymogen granules to the ductal lumen by exocytic mechanisms and 2) enzymatic release of GPI-anchored GP-2 from the luminal membranes, a kinetic process that appears to be regulated by secretin- or carbachol-induced secretion of bicarbonate.

Effects of in vivo cholinergic stimulation of rat exocrine pancreas

1983 ◽  
Vol 244 (6) ◽  
pp. G623-G629
Author(s):  
G. Adler ◽  
G. Gerhards ◽  
J. Schick ◽  
G. Rohr ◽  
H. F. Kern
Keyword(s):  
Dose Response ◽  
Exocrine Pancreas ◽  
Pancreatic Enzyme ◽  
Target Cells ◽  
Response Curves ◽  
Cholinergic Agent ◽  
Rat Exocrine Pancreas ◽  
Biphasic Dose Response

Peptide and cholinergic secretagogues both produce biphasic dose-response curves for pancreatic enzyme secretion in vitro: supraoptimal doses result in submaximal secretory responses. We compared the effects of maximal and supramaximal doses of a cholinergic agent (carbachol) on rat exocrine pancreas in vivo. In conscious rats, volume and enzyme output were measured from the cannulated pancreatic duct during infusion of carbachol for 3 h. Infusion of 5 X 10(-7) mol . kg-1 . h-1 carbachol caused optimal stimulation, whereas a supraoptimal dose (5 X 10(-6) mol . kg-1 . h-1) resulted in submaximal response. Similar results were achieved when discharge of amylase and protein synthesis was determined in vitro after carbachol in vivo. Supraoptimal doses of carbachol increased serum amylase and enhanced acinar cell lysosomal activity in the Golgi area. The latter appeared to induce fusion of zymogen granules, which resulted in cytoplasmic vacuoles. The in vivo results corroborate in vitro findings of a biphasic dose-response relationship for carbachol and demonstrate destructive effects of supraoptimal concentrations on target cells.

Fat-induced changes of the integrity of rat exocrine pancreas measured in vivo and in vitro

1998 ◽  
Vol 114 ◽  
pp. A448
Author(s):  
P. Chowdhury ◽  
M. Nishikawa ◽  
G.T. Blevins ◽  
P.L. Rayford
Keyword(s):  
Exocrine Pancreas ◽  
Rat Exocrine Pancreas ◽  
Induced Changes

In vivo rat pancreatic acinar cell function during supramaximal stimulation with caerulein

1985 ◽  
Vol 249 (6) ◽  
pp. G702-G710 ◽  
Author(s):  
A. Saluja ◽  
I. Saito ◽  
M. Saluja ◽  
M. J. Houlihan ◽  
R. E. Powers ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Intracellular Transport ◽  
Cell Function ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Zymogen Granule ◽  
Zymogen Granules ◽  
Morphological Studies ◽  
Supramaximal Stimulation

Infusion of a supramaximal dose of caerulein results in acute interstitial pancreatitis in rats. We report studies of in vivo pancreatic acinar cell function during the initial 3.5 h of supramaximal stimulation with caerulein (5 micrograms X kg-1 X h-1). Amino acid [( 3H]phenylalanine) uptake was not altered, and there was no change in the rate or extent of protein synthesis or in intracellular transport of in vivo pulse-labeled proteins from microsome to zymogen granule-enriched fractions. However, the discharge of labeled protein was markedly inhibited. Radioautographic studies indicated that the pulse-labeled proteins retained in the gland were not located extracellularly but had accumulated within acinar cells, with a preferential distribution at the cell apex (presumably in zymogen granules) and in large vacuoles that form within the cell during hyperstimulation. Supramaximal stimulation with caerulein also caused increasing amounts of amylase and labeled proteins to be recovered in the postmicrosomal fraction. These findings suggest that supramaximal stimulation causes digestive enzymes to become localized in organelles that are fragile and subject to disruption during tissue homogenization. These organelles may be the vacuoles noted in morphological studies and believed to represent immature condensing vacuoles and/or crinophagic vacuoles.

Ethanol differentially regulates NF-κB activation in pancreatic acinar cells through calcium and protein kinase C pathways

2004 ◽  
Vol 286 (2) ◽  
pp. G204-G213 ◽  
Author(s):  
Anna S. Gukovskaya ◽  
Saeed Hosseini ◽  
Akihiko Satoh ◽  
Jason H. Cheng ◽  
Kyung J. Nam ◽  
...  
Keyword(s):  
Acinar Cells ◽  
Inhibitory Effect ◽  
Pancreatic Acinar Cells ◽  
Alcoholic Pancreatitis ◽  
Pancreatic Acini ◽  
Intracellular Ca ◽  
Ethanol Feeding ◽  
Ethanol Ethanol

Mechanisms of alcoholic pancreatitis remain unknown. Previously, we showed that ethanol feeding sensitizes rats to pancreatitis caused by CCK-8, at least in part, by augmenting activation of the proinflammatory transcription factor NF-κB. To elucidate the mechanism of sensitization, here we investigate the effect of ethanol on Ca2+- and PKC-mediated pathways of CCK-induced NF-κB activation using an in vitro system of rat pancreatic acini incubated with ethanol. Ethanol augmented CCK-8-induced activation of NF-κB, similar to our in vivo findings with ethanol-fed rats. In contrast, ethanol prevented NF-κB activation caused by thapsigargin, an agent that mobilizes intracellular Ca2+ bypassing the receptor. Pharmacological analysis showed that NF-κB activation by thapsigargin but not by CCK-8 is mediated through the calcineurin pathway and that the inhibitory effect of ethanol on the thapsigargin-induced NF-κB activation could be through inhibiting this pathway. Ethanol augmented NF-κB activation induced by the phorbol ester PMA, a direct activator of PKC. Inhibitory analysis demonstrated that Ca2+-independent (novel and/or atypical) PKC isoforms are involved in NF-κB activation induced by both CCK-8 and PMA in cells treated and not treated with ethanol. The results indicate that ethanol differentially affects the Ca2+/calcineurin- and PKC-mediated pathways of NF-κB activation in pancreatic acinar cells. These effects may play a role in the ability of ethanol to sensitize pancreas to the inflammatory response and pancreatitis.

scholarly journals DNA SYNTHESIS, MITOSIS, AND DIFFERENTIATION IN PANCREATIC ACINAR CELLS IN VITRO

1964 ◽  
Vol 20 (3) ◽  
pp. 415-433 ◽  
Author(s):  
Norman K. Wessells
Keyword(s):  
Thymidine Incorporation ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Zymogen Granule ◽  
Peripheral Cell ◽  
Daughter Cells ◽  
Central Regions ◽  
Pancreatic Epithelium

Pieces of mouse embryonic pancreatic epithelium cultured in an inductive situation in vitro, or when examined at critical times in vivo, show a gradient of zymogen granule accumulation. Cells located internally in explants, or in central acini in vivo, show this overt differentiation first. As the epithelia age, the more peripheral cell population proceeds in a similar differentiation. Observations of autoradiograms of H3-thymidine-labeled tissues indicate that the first cells which cease incorporating the DNA-precursor are in the central regions that differentiate first. In older explants, thymidine incorporation is largely restricted to the periphery of the tissue as zymogen appears in the internal cells. Evidence suggests that cells or nuclei which have replicated DNA move inward before dividing. Some daughter cells apparently return peripherad to divide again, whereas others remain centrally where they undergo differentiation. During at least the first 24 hours of these maturational changes, mesenchyme has a stimulatory effect upon epithelial thymidine-incorporation frequencies. The presence of a post-DNA-synthetic population is seen in the form of a group of nonlabeling central cells that remains intact in the midst of a labeled epithelium for as long as 48 hours in vitro (from 72 to 120 hours). If explants are treated with 5-bromodeoxyuridine for any 24-hour segment of the 0 to 72-hour period, before the non-incorporating population arises, no subsequent overt zymogen formation occurs. If explants are treated continuously from 72 to 120 hours, on the other hand, zymogen still forms in some internal cells. Presumably, this differentiation is limited to the postmitotic population as revealed in the thymidine autoradiograms.

scholarly journals CELL MEMBRANE RESORPTION IN THE RAT EXOCRINE PANCREAS CELL AFTER IN VIVO STIMULATION OF THE SECRETION, AS STUDIED BY IN VITRO INCUBATION WITH EXTRACELLULAR SPACE MARKERS

1973 ◽  
Vol 57 (1) ◽  
pp. 159-174 ◽  
Author(s):  
J. J. Geuze ◽  
C. Poort
Keyword(s):  
Cell Membrane ◽  
Extracellular Space ◽  
Protein Transport ◽  
Secretory Protein ◽  
Zymogen Granule ◽  
Basal Face ◽  
Rat Exocrine Pancreas ◽  
Pancreas Cell

Pancreatic secretion in the rat was stimulated in vivo by pilocarpine injection causing 90% of the storage granules to be discharged within 2 h. Incubation in vitro with [14C]sorbitol indicated that maximal ingestion of this extracellular space marker occurred 3 h after secretogogue injection. Morphological cell membrane measurements on cells with stimulated secretion revealed a simultaneous decrease in amount of membrane bordering the microvilli at the cell apex, lamellar processes, and infoldings present at the latero-basal face of these cells. In 3-h stimulated cells, having the average zymogen granule content characteristic for that phase of secretion, ferritin treatment in vitro showed that the infoldings and related fragmentation vesicles had ingested ferritin and could consequently be considered as being transport vehicles for redundant cell membrane. During stimulated secretion numerous vesicles and vacuoles appeared in the apical cytoplasm. Part of these structures were postulated to be related to the Golgi complex and were discussed in relation to secretory protein transport. Another part of these structures was assumed to have an endocytotic nature, although they never contained ferritin.

Control of secretory granule interaction and exocytosis in pancreatic cells

1987 ◽  
Vol 7 (5) ◽  
pp. 435-442 ◽  
Author(s):  
E. K. Matthews ◽  
Jane Rogers ◽  
D. B. McKay
Keyword(s):  
In Vitro Study ◽  
Pancreatic Acinar Cell ◽  
Correlation Spectroscopy ◽  
Zymogen Granules ◽  
Interaction Kinetics ◽  
Rat Exocrine Pancreas ◽  
Cell Cytosol ◽  
Kinetics Of

Application of the laser-based technique of photon correlation spectroscopy to an in vitro study of the ionic stability and interaction kinetics of zymogen granules isolated from rat exocrine pancreas is described here. In addition the separation from pancreatic acinar cell cytosol of a factor which stabilizes isolated zymogen granules and inhibits cation-induced granule aggregation is outlined. The basis of this action and the significance of the cytosolic inhibitory factor in the regulation of granule mobility and exocytosis in vivo is discussed.

Effects of chloroquine and methylamine on lysosomal enzyme secretion by rat pancreas

1992 ◽  
Vol 262 (3) ◽  
pp. G439-G444
Author(s):  
T. Hirano ◽  
A. Saluja ◽  
P. Ramarao ◽  
M. M. Lerch ◽  
M. L. Steer
Keyword(s):  
Lysosomal Enzyme ◽  
Cathepsin B ◽  
Secretory Pathway ◽  
Amylase Secretion ◽  
Zymogen Granule ◽  
Lysosomal Hydrolases ◽  
Pancreatic Acini ◽  
Lysosomotropic Agents

In vivo pancreatic secretion of the lysosomal hydrolase cathepsin B was found to be increased by infusion of the secretagogue caerulein. The basal as well as caerulein-stimulated in vivo rate of cathepsin B was further increased by infusion of either chloroquine or methylamine while neither the basal nor the secretagogue-stimulated rates of amylase secretion were altered by the lysosomotropic agents. These observations indicate that neutralization of the acidic prelysosomal compartment by administration of lysosomotropic agents results in lysosomal enzyme entry, by default, into the regulated secretory pathway. In vitro stimulation of pancreatic acini with caerulein was also found to stimulate cathepsin B secretion. That in vitro rate of cathepsin B secretion stimulated by caerulein was not increased in acini prepared from animals infused with caerulein, chloroquine, or methylamine, but the in vitro rate of cathepsin B secretion stimulated by caerulein was increased in acini prepared from animals infused with caerulein plus either chloroquine or methylamine. Under these conditions, redistribution of cathepsin B from the lysosome-enriched to the zymogen granule-enriched subcellular fraction was noted, and lysosomal enzyme-containing organelles became increasingly fragile. These observations indicate that in vivo secretagogue stimulation increases the degree of diversion of lysosomal hydrolases into the regulated secretory compartment when the prelysosomal compartment has been neutralized with lysosomotropic agents.

scholarly journals SYNTHESIS AND MIGRATION OF PROTEINS IN THE CELLS OF THE EXOCRINE PANCREAS AS REVEALED BY SPECIFIC ACTIVITY DETERMINATION FROM RADIOAUTOGRAPHS

1963 ◽  
Vol 16 (1) ◽  
pp. 1-23 ◽  
Author(s):  
H. Warshawsky ◽  
C. P. Leblond ◽  
B. Droz
Keyword(s):  
Specific Activity ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Zymogen Granule ◽  
Zymogen Granules ◽  
The Mean ◽  
And Migration ◽  
Rats And Mice ◽  
Silver Grains ◽  
Golgi Zone

Radioautographs of pancreatic acinar cells were prepared in rats and mice sacrificed at various times after injection of leucine-, glycine-, or methionine-H3. Measurements of radioactivity concentration (number of silver grains per unit area) and relative protein concentration (by microspectrophotometry of Millon-treated sections) yielded the mean specific activity of proteins in various regions of the acinar cells. The 2 to 5 minute radioautographs as well as the specific activity time curves demonstrate protein synthesis in ergastoplasm. From there, most newly synthesized proteins migrate to and accumulate in the Golgi zone. Then they spread to the whole zymogen region and, finally, enter the excretory ducts. An attempt at estimating turnover times indicated that two classes of proteins are synthesized in the ergastoplasm: "sedentary" with a slow turnover (62.5 hours) and "exportable" with rapid turnover (4.7 minutes). It is estimated that the exportable proteins spend approximately 11.7 minutes in the Golgi zone where they are built up into zymogen granules, and thereafter 36.0 minutes as fully formed zymogen granules, before they are released outside the acinar cell as pancreatic secretion. The mean life span of a zymogen granule in the cell is estimated to be 47.7 minutes.

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