Receptor-mediated internalization and secretion of cholecystokinin into rat pancreatic duct fluid

We measured cholecystokinin (CCK) in pancreatic duct secretions (PDS) after infusion of different amounts of CCK-8 (the C-terminal octapeptide of cholecystokinin) into rats. Injection of 23, 46, and 92 ng of CCK-8 increased immunoreactive cholecystokinin in PDS by 3-, 13-, and 28-fold above basal levels within 30 min. Continuous intravenous infusion of CCK-8 (50 ng/min) into rats for 30 min, followed by a 30-min rest period, and then a final infusion of peptide for another 30 min increased CCK in PDS only during the final period by 12-fold to 500 pg/30 min. Neither gastrin nor oxidized CCK-8 were detected in PDS after intravenous infusion of each peptide. Administration of proglumide (ip), a CCK receptor antagonist, during continuous CCK infusion significantly reduced immunoreactive CCK levels in PDS to 2% of the control group (P less than or equal to 0.01). CCK was also rapidly internalized into dispersed pancreatic acinar cells in a temperature-dependent fashion, and this process was inhibited by proglumide. The above data suggest that CCK in PDS reflects a peptide-specific process that is receptor mediated. We propose that circulating cholecystokinin binds to specific receptors on pancreatic acinar cells, is internalized, and is then secreted into pancreatic duct fluid.

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Effects of short-term administration of the CCK receptor antagonist, KSG-504, on regeneration of pancreatic acinar cells in acute pancreatitis in rats

Journal of Gastroenterology ◽

10.1007/bf02347566 ◽

1995 ◽

Vol 30 (4) ◽

pp. 493-499 ◽

Cited By ~ 1

Author(s):

Yoshiaki Okumura ◽

Hisayuki Inoue ◽

Yoshihide Fujiyama ◽

Tadao Bamba

Keyword(s):

Acute Pancreatitis ◽

Receptor Antagonist ◽

Acinar Cells ◽

Pancreatic Acinar Cells ◽

Short Term ◽

Term Administration ◽

Cck Receptor Antagonist

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Quantitative electron microscope autoradiographs of 125I-cholecystokinin in pancreatic acini

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1982.243.4.g291 ◽

1982 ◽

Vol 243 (4) ◽

pp. G291-G296 ◽

Cited By ~ 2

Author(s):

J. A. Williams ◽

H. Sankaran ◽

E. Roach ◽

I. D. Goldfine

Keyword(s):

Endoplasmic Reticulum ◽

Electron Microscope ◽

Specific Binding ◽

Acinar Cells ◽

Pancreatic Acinar Cells ◽

Pancreatic Acini ◽

Time Points ◽

Basolateral Plasma Membrane ◽

Specific Receptors ◽

Silver Grains

To morphologically evaluate the interaction of cholecystokinin (CCK) with its receptors on pancreatic acinar cells, we incubated isolated mouse acini at 37 degrees C with radioiodinated CCK and then prepared quantitative electron microscope autoradiographs. Specific binding of CCK to acini was one-half maximal at 2 min of incubation and maximal after 10 min. The cell-associated radioactivity was extracted and analyzed on Sephadex G-50. After 2 min, 90% of the total cellular radioactivity remained as intact CCK; after 30 min, the intact radioactivity decreased to 65% of total. At 2 min, the fraction of bound hormone that fixed to acini was 84% of total; this amount decreased to 78% after 30 min. Thus, the majority of radioactivity in the autoradiographs at both time points was intact CCK; however, at 30 min, a small amount was also degraded hormone. After both 2 and 30 min of incubation, silver grains were highly concentrated over the basolateral plasma membrane. A significant number of grains were in the cell interior at both time points, increasing from 13% of total grains at 2 min to 42% at 30 min. At both times, the largest fraction of internalized grains was localized over the endoplasmic reticulum. At 30 min, a significant concentration of CCK grains was observed over multivesicular bodies. The present study demonstrates, therefore, that CCK binds to specific receptors on the basolateral surface of pancreatic acinar cells. After binding, the hormone is internalized, locates predominantly on the endoplasmic reticulum, and is then degraded.

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Sorafenib-induced loss of polarity of zymogen granules in pancreatic acinar cells.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.236 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 236-236

Author(s):

Tatsuo Ito ◽

Ryuichiro Doi ◽

Shinji Uemoto

Keyword(s):

Acute Pancreatitis ◽

Kinase Inhibitor ◽

Pancreatic Enzyme ◽

Acinar Cells ◽

In Vivo Studies ◽

Pancreatic Acinar Cells ◽

Control Group ◽

Amylase Level ◽

Zymogen Granules ◽

Tissue Samples

236 Background: Sorafenib is an oral multi-kinase inhibitor which is regarded as a key drug for HCC and RCC. It has been unexpectedly found that the compound causes an increase of serum pancreatic enzyme levels without clinically recognized pancreatitis. The reason for this event is not well understood yet. The aim of this study was to clarify the mechanisms involved in this phenomenon. Methods: Eight-week old BALB/cA male mice were used in in vivo studies. Sorafenib tosylate was administered per os once daily at a dose of 150 mg/kg body weight. Control mice were given vehicle alone. Mice were sacrificed 24 hr after 1-, 2-, 3- and 7-day administration of the compound, and blood samples and pancreatic tissue samples were obtained (n=5 for each group). The tissue samples were used for hematoxylin and eosin (HE) staining, immunohistochemistry, electron microscopy (EM), western blot and RT-quantitative PCR studies. Results: Serum amylase levels were elevated after sorafenib administration. The amylase level hit the peak after 2-day administration, and then gradually decreased. By HE staining, the control group without sorafenib showed a basophilic stained area in the baso-lateral site of the acinar cells. In contrast, the acinar cytoplasm after 2-day administration of sorafenib was totally eosinophilic. The typical findings of acute pancreatitis were not seen in the both group. By EM examination, zymogen granules (ZGs) of the sorafenib group spread into basal site of the acinar cells. ZGs mounted up on both of apical and baso-lateral plasma membrane and showed exocytosis. The levels of amylase mRNA were not elevated by sorafenib. In addition the expression of N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) proteins was not changed. Conclusions: The results suggest that the amount of acinar amylase production was not changed but the distribution of ZGs was altered by sorafenib. Sorafenib seemed to cause temporary loss of polarity of ZGs secretion in acinar cells by blocking apical exocytosis. Acute pancreatitis was not evident; thus the current model was not similar to the pancreatitis model caused by the supra-maximal secretagogue stimulation which blocks the apical exocytosis.

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E4An Ultrastructural Study by Transmission Electron Microscope of Exocrine Pancreatic Cells in Diabetic Rats Treated with Herbal Combination

Baghdad Science Journal ◽

10.21123/bsj.2019.16.4(suppl.).0966 ◽

2019 ◽

Vol 16 (4(Suppl.)) ◽

pp. 0966

Author(s):

Maysaa Adil Hadi

Keyword(s):

Acinar Cells ◽

Diabetic Rats ◽

Degenerative Changes ◽

Pancreatic Acinar Cells ◽

Control Group ◽

Cellular Activity ◽

Pancreatic Acini ◽

Group Iii ◽

Transmission Electron ◽

Ultrathin Sections

The current study was designed to investigate the alterations in the ultrastructure of orgenelles and cellular activity of exocrine pancreatic acini of experimentally induced-diabetic rats and to assess the usefulness of herbal combination supplementation in improving the ultrastructure and cellular activity of exocrine pancreas. The number of albino male rats used were 24 which divided into equally 4 groups; group I: control group, group II: alloxan-induced diabetes mellitus (single intraperitoneal dose of alloxan 120 mg/kg for 3 days), group III: herbal combination treatment composed from the extracts of fenugreek seeds (Trigonella foenum-graecum), black cumin (Nigella sativa) seeds, rhizomes of ginger (Zingiber officinale), leaves of olive (Olea europeae), and seeds of ash (Fraxinus ssp). Each rat given 2.5 ml (0.5 ml from each five mixed plant extracts used) for 2 months. group IV: diabetes was induced as group II and treated with herbal combination as group III for 2 months. The processing for investigating by transmission electron microscopy were carried out for all pancreata taken from all groups. There was significant reduction (p<0.05) in mean of FBG levels in diabetic rats treated with herbal combination (group IV) as compared to diabetic control and could revert FBG to normal value compared to negative control The results of examination of semithin and ultrathin sections in diabetic rats revealed many degenerative changes in the exocrine pancreatic tissue in comparison to control group. These degenerative changes can be summarized as disturbances in the arrangement of pancreatic acinar cells and decreased secretory granules in addition to the vacuolation of cytoplasm and pyknotic nuclei were observed in semithin sections. Moreover, degenerated nuclei, vacuolation of cytoplasm, fragmentation of rough endoplasm reticulum and degranulation of the most pancreatic acinar cells were noticed in ultrathin sections. In contrast, the acinar cells of group administrated with herbal combination only had normal ultrastructure, cellular activity, and nuclei, well-developed rough endoplasmic reticulum with abundant zymogen granules. Also, most of the acinar cells retrieved their normal ultrastructure and cellular activity in diabetic group treated with herbal combination and herbal combination could decrease most of the degenerative changes caused by alloxan-induced diabetes. In conclusion, the daily supplementation with this herbal combination to diabetic rat for 2 months could achieving promising effects due to its cytoprotective influence and showed the ability to decreased degenerative damage in the ultrastructure and cellular activity of exocrine pancreatic acini in type 2 diabetic rats.

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Trypsinogen activation peptide induces HMGB1 release from rat pancreatic acinar cells

Open Medicine ◽

10.1515/med-2017-0043 ◽

2017 ◽

Vol 12 (1) ◽

pp. 293-298 ◽

Cited By ~ 4

Author(s):

Guoliang Wang ◽

Yan Liu ◽

Danhua Dui ◽

Liang Bai ◽

Yao Liu ◽

...

Keyword(s):

Protein Expression ◽

Inflammatory Responses ◽

Ethyl Pyruvate ◽

Acinar Cells ◽

Pancreatic Acinar Cells ◽

Control Group ◽

Trypsinogen Activation ◽

Mrna And Protein Expression ◽

Trypsinogen Activation Peptide ◽

Activation Peptide

AbstractBackgroundThe development of acute pancreatitis (AP) is associated with intracellular events in pancreatic cells, as well as with early and late inflammatory responses; however, their underlying mechanisms remain unclear. This study investigated trypsinogen activation peptide (TAP)-induced release of high mobility group box-l (HMGB1) from pancreatic acinar cells and how ethyl pyruvate (EP) affects this release.MethodologyPancreatic acinar cells from Sprague Dawley rats were divided into control, TAP (administered TAP), and EP (administered TAP and EP) groups. Cells were collected at 3, 6, 12, and 24 hours after TAP administration to detect HMGB1 mRNA and protein levels using quantitative PCR (qPCR) and Western blotting, respectively.ResultsThe TAP and EP groups exhibited higher levels of HMGB1 mRNA and protein expression (P<0.05) than the control group. The HMGB1 mRNA and protein expression levels also increased with prolonged TAP activity (P<0.05)–especially at 12 and 24 hours (P<0.01)–and showed positive correlations with TAP activity duration (3, 6, 12, and 24 hours) (r=0.971, P<0.01; r=0.966, P<0.01, respectively).ConclusionTAP induces HMGB1 release from pancreatic acinar cells. A positive temporal link exists between early TAP activity and late HMGB1 expression in AP, and EP inhibits HMGB1 release.

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