| 1. |
- Ohlsson, Bodil, et al.
(författare)
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Cholecystokinin does not affect the pancreatic contents of epidermal growth factor or its receptor
- 2000
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Ingår i: Pancreas. - 0885-3177. ; 21:4, s. 385-391
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Tidskriftsartikel (refereegranskat)abstract
- Cholecystokinin (CCK) is a hormone with well-known secretory and trophic effects on the pancreas. This also is true for epidermal growth factor (EGF), which acts in a paracrine and autocrine way. The aim was to study the influence of CCK on cell proliferation in rat pancreas with special reference to the expression of EGF, the EGF receptor, and phosphorylated tyrosine. Twenty-four male Sprague-Dawley rats received either one single injection, or injections twice daily for 3 days of 6 microg sulfated CCK-8 (CCK-8S) subcutaneously in the neck. The same number of rats received injections of 1% bovine serum albumin (BSA) in the same way. The rats were killed 1, 3, or 6 hours after the last injection. One hour before killing, they received 50 mg/kg of bromodeoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and in situ hybridization using a probe for EGF mRNA was performed for semiquantification of gene expression. Immunocytochemistry using antibodies against the EGF receptor and phosphotyrosine was performed to examine the expression of the proteins, and against BrdU for measuring the cell proliferation. A single injection of CCK-8S led to hyperCCKemia at 1 and 3 hours afterward. After 6 hours, plasma CCK had returned to the same levels as in control rats. The cell proliferation was unaffected. The rats that received CCK-8S injections for 3 days still had hyperCCKemia 6 hours after the last injection. The cell proliferation was increased by CCK, as indicated by the BrdU labeling. However, neither body weight nor pancreatic weight was affected. In controls, EGF was expressed all over the gland, but its receptor and phosphotyrosine were expressed only in ductal cells and in the islet cells of endocrine pancreas. There was no difference in the pancreatic staining of EGF, its receptor, or phosphotyrosine at the different time points studied. There was no difference in the staining of EGF and its receptor between CCK-8S- and BSA-treated animals, but phosphotyrosine staining was detectable in acinar cells after 3 days of CCK-8S injections. Thus CCK-8S causes hyperCCKemia with ensuing enhanced cell proliferation in rat pancreas. This effect on the cell proliferation seems to be a direct effect of CCK and not mediated by changes in the tissue levels of EGF or its receptor.
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| 2. |
- Ohlsson, Bodil, et al.
(författare)
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Continuous infusion of cholecystokinin leads to down-regulation of the cholecystokinin-A receptor in the rat pancreas
- 2000
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 35:6, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infusion of sulphated cholecystokinin-8 (CCK-8S) in rats transiently increased the proliferation of pancreatic acinar cells, whereas the CCK-A receptor antagonist devazepide decreased such proliferation. This effect ceased after 3 days. CCK-8S or devazepide injected twice daily induced a persistent effect on the cell proliferation involving the major cells of the exocrine pancreas. The aim of this study was to examine the effect of continuous infusion of CCK-8S and devazepide on CCK-A receptor gene expression. METHODS: Male Sprague-Dawley rats received subcutaneous continuous infusion of 5 microg/kg/h CCK-8S, 200 microg/kg/h devazepide, or 1% bovine serum albumin (BSA) by means of osmotic minipumps. The rats were killed after 4 days; I h before being killed they received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and indirect immunofluorescence for BrdU and CCK-A receptor was performed. In situ hybridization to CCK-A receptor mRNA was performed for examination and semiquantification of receptor gene expression. RESULTS: Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40% increase in pancreatic weight. Devazepide did not affect the CCK level but decreased the pancreatic weight by 24% compared with BSA-infused rats. The BrdU labeling indicated that CCK-8S had no effect on cell proliferation. Immunofluorescence for the CCK-A receptor showed a decreased labeling intensity after CCK-8S infusion. The mean optical density of in situ hybridization labeling of the sections from CCK-8S-treated rats was decreased to 37% +/- 3% of that in controls. Devazepide did not affect the CCK-A receptor gene expression. CONCLUSIONS: Continuous stimulation of the CCK-A receptor led to a downregulation of the receptor gene expression in pancreatic acinar cells and decreased labeling of the receptor at immunohistochemistry. The results suggest that down-regulation of the receptor is a protective mechanism against overstimulation.
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| 3. |
- Bergenfelz, A, et al.
(författare)
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Pancreastatin plasma levels in patients with primary hyperparathyroidism
- 2000
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 24:12, s. 83-1579
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Tidskriftsartikel (refereegranskat)abstract
- Pancreastatin, a C-terminally amidated peptide derived from chromogranin A, is known to inhibit insulin secretion, pancreatic enzyme release, and gastric acid secretion. It also inhibits parathyroid hormone (PTH) secretion in animals. The physiologic and clinical relevance of pancreastatin in humans, however, is not known. Because pancreastatin has been found in parathyroid adenomas, we investigated the plasma levels in patients with primary hyperparathyroidism (pHPT). Thirteen patients operated on for solitary parathyroid adenoma were investigated. Plasma levels of pancreastatin and serum levels of ionized calcium and intact PTH were measured before and 6 weeks after operation. In 10 patients the levels were also monitored before and 60 minutes after adenoma excision. The adenomas were investigated for pancreastatin immunoreactivity by immunocytochemistry. The median weight of the excised parathyroid adenoma was 0.64 g (range 0.07-2.00 g). Cells displaying pancreastatin immunoreactivity were present in all adenomas examined and varied in number and immunostaining intensity among and within the adenomas. Intraoperatively, after adenoma excision the levels of PTH and pancreastatin declined (p < 0.01), whereas the levels of ionized calcium did not change (p = 0.96). At the 6-week follow-up the levels of ionized calcium and PTH had decreased compared to the preoperative levels (p < 0.01), and all patients were normocalcemic. In contrast, the pancreastatin levels were not changed (14.5 +/- 6.1 pmol/L preoperatively vs. 12.8 +/- 11.2 pmol/L 6 weeks postoperatively; p = 0.12). In patients with pHPT, pancreastatin is likely to be produced by the parathyroid adenoma. The changes in pancreastatin levels immediately after surgery warrant further investigation.
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| 4. |
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| 5. |
- Ekblad, E., et al.
(författare)
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Neuropeptides in the human appendix - Distribution and motor effects
- 1989
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Ingår i: Digestive Diseases and Sciences. - 0163-2116. ; 34:8, s. 1217-1230
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Tidskriftsartikel (refereegranskat)abstract
- At present our knowledge of enteric peptide-containing neurons in man is limited. In this study we have used human appendices removed at surgery to examine the peptidergic innervation by immunocytochemistry, immunochemistry, and pharmacological in vitro experiments. Immunocytochemistry revealed a variety of peptide-containing nerve fiber populations in the human appendix. VIP/PHI-, VIP/PHI/NPY-, SP/NKA-, galanin-, and enkephalin-containing nerve fibers were numerous; CGRP- and GRP- containing nerve fibers were moderate in number, while only scattered NPY-, enkephalin/BAM-, and somatostatin-containing nerve fibers could be found. No CCK-, dynorphin A-, or dynorphin B- immunoreactive nerve fibers could be detected. The coexistence of VIP/PHI, SP/NKA, and enkaphalin/BAM can be anticipated from the known sequence of their respective precursors. However, the coexistence of VIP/PHI and NPY was unexpected but corroborates previous observations in other species. Interestingly, SP and CGRP did not seem to coexist in nerve fibers of the human appendix. Immunochemistry (RIA and HPLC) confirmed the presence of VIP, NPY, SP, galanin, CGRP, GRP, enkephalin, and somatostatin. Motor activity studies suggest that acetylcholine plays a major role in the electrically evoked contractions, since atropine suppressed these contractions. Galanin (10-8-10-6 M) and GRP (10-9-10-7 M) caused concentration-dependent contractions that were unaffected by tetrodotoxin and thus probably reflect a direct action on smooth muscle receptors. GRP (10-9 M) enhanced the electrically induced cholinergic contraction (to 193±24%), while met-enkephalin (10-6 M) reduced it (to 54±6%). Both peptides failed to affect the contractile response to exogenous acetylcholine and probably act to modulate the release of acetylcholine. NPY, VIP, CGRP, SP, and somatostatin failed to induce contraction or to affect the electrically evoked contractions.
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| 6. |
- Friis-Hansen, L, et al.
(författare)
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Antral G-cell in gastrin and gastrin-cholecystokinin knockout animals
- 2005
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 321:1, s. 141-146
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Tidskriftsartikel (refereegranskat)abstract
- The antral hormone gastrin is the key regulator of gastric acid secretion, mucosal growth and differentiation. Gastrin is synthesized in the endocrine G-cells in the antroduodenal mucosa. We have now examined the way in which the loss of gastrin alone or gastrin plus cholecystokinin (CCK) affects the antral G-cell. Immunohistochemistry, radioimmunoassay and quantitative real-time polymerase chain reaction techniques were employed to examine the expression of genes belonging to the G-cell secretory pathway in gastrin and gastrin-CCK knockout mice. Transmission electron microscopy was used to examine the ultrastructure of the G-cells. The number of G-cells increased but the secretory granules were few and abnormally small in the G-cells of both mouse models compared with wildtypes. Thus, gastrin is not necessary for the formation of G-cells as such but the lack of gastrin reduces the number and size of their secretory granules suggesting that gastrin is vital for the formation and/or maintenance of secretory granules in G-cells.
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| 7. |
- Friis-Hansen, Lennart, et al.
(författare)
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Reduced ghrelin, IAPP and PYY expression in the stomach of gastrin-cholecystokinin knockout mice.
- 2005
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 146:10, s. 4464-4471
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Tidskriftsartikel (refereegranskat)abstract
- The antral hormone gastrin and its intestinal relative, cholecystokinin (CCK), are pivotal in the regulation of gastric functions. Other gastric hormones like ghrelin, peptide YY (PYY), and islet amyloid polypeptide (IAPP), however, also contribute to the regulation of acid secretion, motility, and feeding. Because gastrin and CCK are crucial for gastric homeostasis, we examined how loss of gastrin alone and gastrin plus CCK affected the expression of ghrelin, IAPP, and PYY and ghrelin secretion. The expression of ghrelin, IAPP, and PYY and the CCK-A receptor genes were examined in both gastrin and gastrin-CCK double-knockout (KO) mice using immunocytochemistry and quantitative RT-PCR. Ghrelin concentrations in plasma were measured using RIA. Gastrin and CCK were infused in gastrin-CCK KO mice using osmotic minipumps. The number of ghrelin cells and ghrelin gene expression were unaffected, albeit the ghrelin cells were located closer to the base of the glands in both KO mouse strains when freely fed. However, lack of both gastrin and CCK attenuated fasting-induced ghrelin expression and secretion. Fundic ghrelin cells expressed the CCK-A receptor, and ghrelin expression increased after CCK infusion. Furthermore, gastric IAPP and PYY expression as well as the number of IAPP- and PYY-containing cells were reduced in both gastrin and gastrin-CCK KO mice. Gastrin infusion increased gastric IAPP but not PYY expression. In conclusion, lack of gastrin plus CCK but not gastrin alone reduced ghrelin secretion in response to fasting through both direct and indirect mechanisms. Both gastrin and combined gastrin-CCK deficiency reduced the gastric IAPP and PYY expression.
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