Regulation of pancreatic exocrine secretion in vitro : the action of secretagogues

1981 ◽  
Vol 296 (1080) ◽  
pp. 17-26 ◽  
Keyword(s):  
Acinar Cells ◽  
Exocrine Secretion ◽  
Mechanisms Of Action ◽  
Enzyme Secretion ◽  
Pancreatic Acinar Cells ◽  
Wide Range ◽  
Pancreatic Exocrine ◽  
Final Effect ◽  
Stimulation Of

Pancreatic acinar cells possess two functionally distinct mechanisms by which secretagogues can increase enzyme secretion. One mechanism is mediated by mobilization of cellular calcium and can be activated by any one of four different classes of receptors. The other mechanism is mediated by cyclic AMP and can be activated by either of two different classes of receptors. In addition to stimulating enzyme secretion, a secretagogue can cause potentiation of secretion, desensitization to the subsequent stimulation caused by the same or other secretagogues as well as residual stimulation of enzyme secretion. Although each class of secretagogue receptors can cause the same final effect, stimulation of enzyme secretion, the existence of multiple classes of receptors and the different mechanisms of action endow the acinar cell with a wide range of patterns of response depending on which of the several classes of receptors are activated.

Cholecystokinin at physiological levels evokes pancreatic enzyme secretion via a cholinergic pathway

1992 ◽  
Vol 263 (1) ◽  
pp. G102-G107 ◽  
Author(s):  
H. C. Soudah ◽  
Y. Lu ◽  
W. L. Hasler ◽  
C. Owyang
Keyword(s):  
Acetylcholine Release ◽  
Pancreatic Enzyme ◽  
Exocrine Secretion ◽  
Cholinergic Innervation ◽  
Enzyme Secretion ◽  
Healthy Humans ◽  
Cholinergic Pathway ◽  
Pancreatic Enzyme Secretion ◽  
Stimulation Of

The mechanism by which physiological concentrations of cholecystokinin (CCK) evoke pancreatic exocrine secretion in humans was investigated. CCK octapeptide (CCK-8) dose dependently increased trypsin and lipase output in healthy humans. Atropine inhibited CCK-8 (10 ng.kg-1.h-1)-stimulated trypsin output by 84.0 +/- 7.7% and lipase output by 78.6 +/- 9.2%. The inhibition with atropine was much less with a CCK-8 dose of 40 ng.kg-1.h-1 (41.8 +/- 6.6% for trypsin and 46.3 +/- 7.3% for lipase). CCK-8 at 10 ng.kg-1.h-1 produced plasma CCK levels similar to postprandial levels (6.0 +/- 1.3 vs. 6.9 +/- 0.8 pM), whereas the 40-ng.kg-1.h-1 dose produced supraphysiological levels (18.4 +/- 3.1 pM). To evaluate if CCK might act via stimulation of cholinergic nerves, in vitro studies were performed using rat pancreas. CCK-8 (10 nM-10 microM) stimulated [3H]acetylcholine release from pancreatic lobules that was blocked by tetrodotoxin, a calcium-free medium, and the CCK antagonist L364,718. In conclusion, CCK-stimulated pancreatic enzyme secretion is dependent on cholinergic neural and noncholinergic pathways. In humans, CCK infusions, which produce plasma CCK levels similar to those seen postprandially, stimulate the pancreas predominantly via a pathway dependent on cholinergic innervation. Correlative in vitro experiments suggest that CCK may act by stimulation of neural acetylcholine release. In contrast, supraphysiological CCK infusions act in part via noncholinergic pathways.

Intracellular Ca2+ in pancreatic acinar cells: Regulation and role in stimulation of enzyme secretion

1987 ◽  
Vol 7 (4) ◽  
pp. 333-344 ◽  
Author(s):  
Robert L. Dormer ◽  
Graham R. Brown ◽  
Claire Doughney ◽  
Margaret A. McPherson
Keyword(s):  
Endoplasmic Reticulum ◽  
Pancreatic Enzyme ◽  
Acinar Cells ◽  
Enzyme Secretion ◽  
Pancreatic Acinar Cells ◽  
Current Evidence ◽  
Primary Role ◽  
Direct Demonstration ◽  
Pancreatic Enzyme Secretion ◽  
Stimulation Of

Evidence for a primary role for intracellular Ca2+ in the stimulation of pancreatic enzyme secretion is reviewed. Measurements of cytoplasmic free Ca2+ concentration have allowed direct demonstration of its importance in triggering enzyme secretion and defined the concentration range over which membrane Ca2+ pumps must work to regulate intracellular Ca2+. Current evidence suggests a key role for the Ca2+ Mg-ATPase of rough endoplasmic reticulum in regulating intracellular Ca2+ and accumulating a Ca2+ store which is released by the action of inositol-l,4,5 trisphosphate following stimulation of secretion.

scholarly journals MFG-E8 Maintains Cellular Homeostasis by Suppressing Endoplasmic Reticulum Stress in Pancreatic Exocrine Acinar Cells

2022 ◽  
Vol 9 ◽  
Author(s):  
Yifan Ren ◽  
Wuming Liu ◽  
Jia Zhang ◽  
Jianbin Bi ◽  
Meng Fan ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Milk Fat ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Cellular Homeostasis ◽  
Pancreatic Exocrine

Excessive endoplasmic reticulum (ER) stress contributes significantly to the pathogenesis of exocrine acinar damage in acute pancreatitis. Our previous study found that milk fat globule EGF factor 8 (MFG-E8), a lipophilic glycoprotein, alleviates acinar cell damage during AP via binding to αvβ3/5 integrins. Ligand-dependent integrin-FAK activation of STAT3 was reported to be of great importance for maintaining cellular homeostasis. However, MFG-E8’s role in ER stress in pancreatic exocrine acinar cells has not been evaluated. To study this, thapsigargin, brefeldin A, tunicamycin and cerulein + LPS were used to induce ER stress in rat pancreatic acinar cells in vitro. L-arginine- and cerulein + LPS-induced acute pancreatitis in mice were used to study ER stress in vivo. The results showed that MFG-E8 dose-dependently inhibited ER stress under both in vitro and in vivo conditions. MFG-E8 knockout mice suffered more severe ER stress and greater inflammatory response after L-arginine administration. Mechanistically, MFG-E8 increased phosphorylation of FAK and STAT3 in cerulein + LPS-treated pancreatic acinar cells. The presence of specific inhibitors of αvβ3/5 integrin, FAK or STAT3 abolished MFG-E8’s effect on cerulein + LPS-induced ER stress in pancreatic acinar cells. In conclusion, MFG-E8 maintains cellular homeostasis by alleviating ER stress in pancreatic exocrine acinar cells.

Effects of oncogenic K-ras on pancreatic acinar cells In vitro

2001 ◽  
Vol 120 (5) ◽  
pp. A722-A722
Author(s):  
Y BI ◽  
C LOGSDON
Keyword(s):  
Acinar Cells ◽  
Pancreatic Acinar Cells

Activated Pancreatic Stellate Cells Promote Acinar Duct Metaplasia by Disrupting Mitochondrial Respiration and Releasing Reactive Oxygen Species

2021 ◽  
Vol 01 ◽  
Author(s):  
Hong Xiang ◽  
Fangyue Guo ◽  
Qi Zhou ◽  
Xufeng Tao ◽  
Deshi Dong
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Respiration ◽  
Reactive Oxygen ◽  
Acinar Cells ◽  
Stellate Cells ◽  
Pancreatic Fibrosis ◽  
Pancreatic Stellate Cells ◽  
Pancreatic Acinar Cells ◽  
Oxygen Species

Background: Chronic pancreatitis (CP) is a long-term risk factor for pancreatic ductal adenocarcinoma (PDAC), and both diseases share a common etiology. The activation of Pancreatic stellate cells (PaSCs) caused by inflammation of the chronic pancreas plays a pivotal role in the pathology of pancreatic fibrosis and the malignant phenotype of PDAC. However, the central role of activated PaSCs in acinar-to-ductal metaplasia (ADM) remains unknown. Objective: In the present study, we investigated the link between pancreatic fibrosis and ADM and the possible underlying mechanism. Methods: A caerulein-treated mouse CP model was established, and Masson trichrome histochemical stain and transmission electron microscope (TEM) were used to observe stromal fibrosis and cell ultrastructure, respectively. The expression of amylase and cytokeratin 19 (CK19), mitochondria respiration, and reactive oxygen species (ROS) were detected in vitro in the co-culture model of primary pancreatic acinar cells and PaSCs. Results: The activation of PaSCs and pancreatic fibrosis were accompanied by ADM in pancreatic parenchyma in caerulein-treated mice, which was verified by the co-cultivation experiment in vitro. Furthermore, we showed that activated PaSCs promote ADM by disrupting mitochondrial respiration and releasing ROS. The expression of inflammation-and ADM-related genes, including S100A8, S100A9, and CK19, was observed to be up-regulated in pancreatic acinar cells in the presence of activated PaSCs. The expression of S100A9 and CK19 proteins was also up-regulated in acinar cells co-cultured with activated PaSCs. Conclusion: The manipulation of mitochondrial respiration and ROS release is a promising preventive and/or therapeutic strategy for PDAC, and S100A9 is expected to be a therapeutic target to block the ADM process induced by the activation of PaSCs.

CCK independently activates intracellular trypsinogen and NF-κB in rat pancreatic acinar cells

2001 ◽  
Vol 280 (3) ◽  
pp. C465-C472 ◽  
Author(s):  
Bing Han ◽  
Baoan Ji ◽  
Craig D. Logsdon
Keyword(s):  
Chinese Hamster ◽  
Acinar Cells ◽  
Nuclear Factor Κb ◽  
Pancreatic Acinar Cells ◽  
Pyrrolidine Dithiocarbamate ◽  
Trypsinogen Activation ◽  
Independent Events ◽  
Dna Binding Assay ◽  
The Relationship ◽  
Stimulation Of

In the cholecystokinin (CCK) hyperstimulation model of acute pancreatitis, two early intracellular events, activation of trypsinogen and activation of nuclear factor-κB (NF-κB), are thought to be important in the development of the disease. In this study, the relationship between these two events was investigated. NF-κB activity was monitored by using a DNA binding assay and mob-1 chemokine gene expression. Intracellular trypsin activity was measured by using a fluorogenic substrate. Protease inhibitors including FUT-175, Pefabloc, and E-64d prevented CCK stimulation of intracellular trypsinogen and NF-κB activation. Likewise, the NF-κB inhibitors pyrrolidine dithiocarbamate and N-acetyl-l-cysteine inhibited CCK stimulation of NF-κB and intracellular trypsinogen activation. These results suggested a possible codependency of these two events. However, CCK stimulated NF-κB activation in Chinese hamster ovary-CCKAcells, which do not express trypsinogen, indicating that trypsin is not necessary for CCK activation of NF-κB. Furthermore, adenovirus-mediated expression in acinar cells of active p65 subunits to stimulate NF-κB, or of inhibitory κB-α molecules to inhibit NF-κB, did not affect either basal or CCK-mediated trypsinogen activation. Thus trypsinogen and NF-κB activation are independent events stimulated by CCK.

scholarly journals Organotypic Culture of Acinar Cells for the Study of Pancreatic Cancer Initiation

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2606
Author(s):  
Carlotta Paoli ◽  
Alessandro Carrer
Keyword(s):  
Pancreatic Cancer ◽  
Ex Vivo ◽  
Acinar Cells ◽  
Lineage Tracing ◽  
Metabolic Reprogramming ◽  
Pancreatic Acinar Cells ◽  
Ductal Adenocarcinoma ◽  
Molecular Features ◽  
The Impact

The carcinogenesis of pancreatic ductal adenocarcinoma (PDA) progresses according to multi-step evolution, whereby the disease acquires increasingly aggressive pathological features. On the other hand, disease inception is poorly investigated. Decoding the cascade of events that leads to oncogenic transformation is crucial to design strategies for early diagnosis as well as to tackle tumor onset. Lineage-tracing experiments demonstrated that pancreatic cancerous lesions originate from acinar cells, a highly specialized cell type in the pancreatic epithelium. Primary acinar cells can survive in vitro as organoid-like 3D spheroids, which can transdifferentiate into cells with a clear ductal morphology in response to different cell- and non-cell-autonomous stimuli. This event, termed acinar-to-ductal metaplasia, recapitulates the histological and molecular features of disease initiation. Here, we will discuss the isolation and culture of primary pancreatic acinar cells, providing a historical and technical perspective. The impact of pancreatic cancer research will also be debated. In particular, we will dissect the roles of transcriptional, epigenetic, and metabolic reprogramming for tumor initiation and we will show how that can be modeled using ex vivo acinar cell cultures. Finally, mechanisms of PDA initiation described using organotypical cultures will be reviewed.

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