| 1. |
- Andersson, K, et al.
(författare)
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Depletion of enterochromaffin-like cell histamine increases histidine decarboxylase and chromogranin A mRNA levels in rat stomach by a gastrin-independent mechanism.
- 1996
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Ingår i: Scandinavian Journal of Gastroenterology. - 1502-7708. ; 31:10, s. 65-959
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrin activates histidine decarboxylase (HDC) and increases HDC and chromogranin A (CGA) mRNA levels in histamine-producing enterochromaffin-like (ECL) cells in the rat stomach. We have studied how histamine depletion by subcutaneous infusion of the HDC inhibitor alpha-fluoromethyl-histidine (alpha-FMH) affects how ECL cells respond to hypergastrinemia in terms of HDC and CGA mRNA levels. METHODS: In one experiment rats received alpha-FMH for 24 h. In another experiment rats received alpha-FMH, omeprazole (perorally), or a combination of the two drugs for 10 days. In a third experiment antrectomized rats were treated with alpha-FMH for 48 h. The circulating gastrin level, oxyntic mucosal histamine concentration, HDC activity, and HDC and CGA mRNA levels were determined. RESULTS: alpha-FMH for 24 h increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. alpha-FMH for 10 days increased the serum gastrin concentration twofold. alpha-FMH + omeprazole resulted in the same serum gastrin concentration as after omeprazole alone (eightfold increase). HDC mRNA levels were higher after alpha-FMH + omeprazole than after omeprazole alone. alpha-FMH alone induced an HDC mRNA level that was similar in magnitude to that observed after omeprazole, although the serum gastrin concentration after alpha-FMH was much lower. In antrectomized rats alpha-FMH increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. CONCLUSION: ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.
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| 2. |
- Andersson, K, et al.
(författare)
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Effect of a-fluoromethylhistidine-evoked histamine depletion on ultrastructure of endocrine cells in acid-producing mucosa of stomach in mouse, rat and hamster
- 1996
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Ingår i: Cell and Tissue Research. - 1432-0878. ; 286:3, s. 84-375
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Tidskriftsartikel (refereegranskat)abstract
- The oxyntic mucosa of the mammalian stomach is rich in endocrine cells, such as ECL cells, A-like cells, somatostatin cells, D1/P cells and, in some species, enterochromaffin cells. The various endocrine cell types can be distinguished on the basis of their characteristic cytoplasmic granules and vesicles. The ECL cells contain numerous large secretory vesicles and relatively few, small electron-dense granules and small clear microvesicles. We have suggested that in the rat the ECL cells contain most of the gastric histamine with the secretory vesicles as the major histamine storage site in these cells. alpha-Fluoromethylhistidine is an irreversible inhibitor of histidine decarboxylase, the histamine-forming enzyme. We have previously shown that this enzyme inhibitor depletes histamine from the ECL cells in the rat and reduces the number of secretory vesicles in the cytoplasm. In the present study, we have examined whether alpha-fluoromethylhistidine affects the ECL cells in other species and whether it affects other types of endocrine cells in the oxyntic mucosa of the rat. Mice, rats and hamsters were treated with the inhibitor (3 mg/kg per h) via minipumps subcutaneously for 24 h. This treatment lowered the oxyntic mucosal histamine concentration by 65-90% and the number and volume density of the secretory vesicles by 85-95% in the ECL cells of the three species examined. In contrast, the number and volume density of granules and microvesicles were not greatly affected. No evidence was found for an effect of alpha-fluoromethylhistidine on A-like cells, somatostatin cells or D1/P cells of the rat stomach, suggesting that, unlike the ECL cells, they do not contain histamine.
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| 3. |
- Andersson, K, et al.
(författare)
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Enterochromaffin-like cells in the rat stomach: effect of depletion. A chemical, histochemical and electron-microscopic study
- 1992
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Ingår i: Cell and Tissue Research. - 1432-0878. ; 270:1, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- In the rat, gastric histamine is stored predominantly in the enterochromaffin-like (ECL) cells, which are located basally in the oxyntic mucosa. The functional significance of histamine in the ECL cells is a matter of speculation. In this study the effect of depletion of histamine on the properties and ultrastructure of the ECL cells was examined. Histamine synthesis was inhibited with alpha-fluoromethylhistidine (3 mg.kg-1.h-1) given via osmotic minipumps over a period of 24 h. The treatment reduced the histidine decarboxylase activity (approximately 20% remaining) and histamine concentration (less than 20% remaining) in the oxyntic mucosa, as well as the intensity of histamine- and chromogranin A-immunostaining in the ECL cells, compared to control rats. The cytoplasmic (secretory) granules/vesicles were greatly reduced in number and size following alpha-fluoromethylhistidine administration. The histamine immunostaining of the mast cells, which occurs at the mucosal surface and in the submucosa, appeared unaffected. We conclude that ECL cell histamine accounts for at least 80% of the total oxyntic mucosal histamine in the rat and that it represents a more mobile pool than mast cell histamine. The reduction in the number and size of the ECL cell granules/vesicles following histamine depletion is in accord with the idea that they represent the storage site for histamine.
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| 4. |
- Andersson, K, et al.
(författare)
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Gastric acid secretion after depletion of enterochromaffin-like cell histamine. A study with a-fluoromethylhistidine in rats
- 1996
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Ingår i: Scandinavian Journal of Gastroenterology. - 1502-7708. ; 31:1, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Histamine is thought to play a central role in the regulation of gastric acid secretion. In the rat oxyntic mucosa most of the histamine is synthesized and stored in enterochromaffin-like (ECL) cells, and the rest resides in mast cells. The present study examines the role of ECL-cell histamine in the control of acid secretion in the intact, conscious rat. METHODS: Rats were treated with alpha-fluoromethylhistidine (alpha-FMH) to inhibit histamine synthesis. alpha-FMH was given by continuous subcutaneous infusion (3 mg/kg/h) for up to 9 days. An additional oral dose of alpha-FMH (50 mg/kg) was given 2 h before each acid secretion test. Acid secretion was studied in pylorus-ligated rats and in chronic gastric fistula rats stimulated with histamine, gastrin-17, or insulin after 2-6 days of alpha-FMH infusion. RESULTS: Treatment with alpha-FMH lowered oxyntic mucosal histamine synthesis by 80%. From previous observations this is thought to reflect depletion of histamine from the ECL cells. The remaining 20% resides in mucosal and submucosal mast cells, which seem to be resistant to alpha-FMH. Basal acid secretion was inhibited by more than 60% after alpha-FMH treatment and by more than 80% by ranitidine. Histamine-stimulated secretion was unaffected by alpha-FMH and abolished by the histamine H2-receptor antagonist ranitidine. The acid response to gastrin-17 was almost abolished in histamine-depleted rats and abolished by ranitidine. Vagally induced acid secretion (provoked by the injection of insulin or by pylorus ligation) was unaffected by alpha-FMH treatment but abolished by ranitidine and by the muscarinic M1-receptor antagonist pirenzepine. CONCLUSION: The results suggest that gastrin stimulates acid secretion by releasing histamine from ECL cells. Vagally induced acid secretion is also dependent on a histaminergic pathway but not on ECL-cell histamine.
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| 5. |
- Andersson, K, et al.
(författare)
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Hyperplasia of histaime-depleted enterochromaffin-like cells in rat stomach using omeprazole and a-fluoromethylhistidine
- 1992
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Ingår i: Gastroenterology. - 1528-0012. ; 103:3, s. 897-904
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Tidskriftsartikel (refereegranskat)abstract
- In the rat, gastric histamine is stored mainly in the enterochromaffinlike cells. Gastrin releases histamine from these cells, and long-term hypergastrinemia results in hyperplasia. The effect of sustained hypergastrinemia on histamine-depleted enterochromaffinlike cells was studied by measuring histidine decarboxylase activity and histamine concentrations and by using quantitative histology. Hypergastrinemia maintained for 6 weeks was induced by inhibition of gastric acid secretion with omeprazole (400 mumol.kg-1.day-1) given orally, and histamine synthesis was inhibited for the same length of time with alpha-fluoromethylhistidine (3 mg.kg-1.h-1) given via osmotic minipumps. In rats given omeprazole alone, the effects of the resulting hypergastrinemia on the enterochromaffinlike cells was reflected in increased histidine decarboxylase activity, increased histamine concentration, and increased number of enterochromaffinlike cells. The general trophic effects on the stomach were seen as increased stomach and oxyntic mucosal weight and increased mucosal thickness. Treatment with alpha-fluoromethylhistidine plus omeprazole markedly reduced the histidine decarboxylase activity and histamine concentration, but the weight of the stomach and oxyntic mucosa, the enterochromaffinlike cell density, and intensity of histidine decarboxylase immunostaining were increased to at least the same extent as after omeprazole alone. These observations indicate that enterochromaffinlike cell histamine is not important for a full expression of gastrin-evoked trophic effects in the stomach.
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| 6. |
- Andersson, Niklas, 1970, et al.
(författare)
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A gene expression fingerprint of mouse stomach ECL cells.
- 2005
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 332:2, s. 404-10
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Tidskriftsartikel (refereegranskat)abstract
- Many of the endocrine cells in the stomach are poorly characterized with respect to physiological significance. In some cases, the anticipated hormone has not yet been identified. Global gene expression analysis of mouse stomach was performed in an attempt to identify the ECL-cell peptide/protein. Specific functional activation (omeprazole-induced hypergastrinaemia) was used as a tool to generate a gene expression fingerprint of the ECL cells. The proposed fingerprint includes 14 genes, among them six are known to be expressed by ECL cells (=positive controls), and some novel ones, which are likely to be ECL-cell-related. The known ECL-cell-related genes are those encoding histidine decarboxylase, chromogranin A and B, vesicular monoamine transporter 2, synaptophysin, and the cholecystokinin-B receptor. In addition, the fingerprint included five genes, which might be involved in the process of secretion and three ESTs with unknown function. Interestingly, parathyroid hormone-like hormone (Pthlh) was identified as a candidate ECL-cell peptide hormone.
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| 7. |
- Andersson, Niklas, 1970, et al.
(författare)
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Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopaenia in the young female rat.
- 2002
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 175:3, s. 695-703
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Tidskriftsartikel (refereegranskat)abstract
- Both ovariectomy (Ovx) and gastrectomy (Gx) induce osteopaenia in rats and humans. While the effect of Ovx has been ascribed to oestrogen deficiency, the underlying mechanism behind Gx is poorly understood. Alendronate, oestrogen and parathyroid hormone (PTH) are known to prevent the osteopaenia induced by Ovx in rats. The purpose of the present study was to determine whether alendronate, oestrogen or PTH could also prevent Gx-evoked osteopaenia. Rats were Ovx-, Gx-, or were sham-operated (Sham) and were then treated with alendronate (50 micro g/kg/day), oestrogen (10 micro g/kg/day) or PTH(1-84) (75 micro g/kg/day) for eight weeks. At sacrifice, serum PTH was unaffected by surgery (Ovx, 64+/-8 pg/ml; Gx, 75+/-13 pg/ml; Sham, 58+/-11 pg/ml). The bone mineral density (BMD) of the fifth lumbar vertebra (L5) was analysed. Ovx and Gx reduced the BMD (ash weight/Volume) of the L5 by 15+/-4% and 22+/-3% respectively. Trabecular BMD and the cortical bone mineral content (BMC) of the femur were assessed using peripheral computed tomography. Both Ovx and Gx markedly reduced trabecular BMD in the metaphyseal area of the distal femur (Ovx, -37+/-7%; Gx, -49+/-7%). The cortical BMC of the femur was only slightly reduced. Alendronate prevented trabecular bone loss after both Ovx and Gx, while oestrogen and PTH prevented trabecular bone loss after Ovx but not after Gx. In conclusion, the bisphosphonate alendronate prevented both Ovx- and Gx-induced trabecular bone loss. In contrast, PTH and oestrogen prevented Ovx-induced but not Gx-induced trabecular bone loss, suggesting that the mechanism behind the trabecular bone loss in Ovx rats differs from that in Gx rats. The results support the notion that the mechanism of action for the bone-sparing effect of these drugs differs. The ability of alendronate, and probably also other bisphosphonates, to prevent Gx-evoked osteopaenia in the rat might be of potential clinical interest when dealing with post-Gx osteopaenia in humans.
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| 8. |
- Andersson, Niklas, 1970, et al.
(författare)
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Pharmacological treatment of osteopenia induced by gastrectomy or ovariectomy in young female rats.
- 2004
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Ingår i: Acta orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470 .- 1651-1964. ; 75:2, s. 201-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both gastrectomy (GX) and ovariectomy (OVX) induce osteopenia in man and experimental animals. The present study addresses the question--can alendronate, estrogen or parathyroid hormone (PTH) be used to treat established GX- or OVX -evoked osteopenia? METHODS: Rats were GX-, OVX- or SHAM-operated 8 weeks before starting the treatment with drugs. Each group was then treated for 8 weeks with 50 microg/kg/day alendronate, 10 microg/kg/day estrogen or 75 microg/kg/day PTH(1-84); n = 8 rats/group. Peripheral Quantitative Computed Tomography (pQCT) was used to measure trabecular bone mineral density (BMD) and various cortical bone parameters. RESULTS: At killing, 16 weeks after surgery, GX and OVX rats had a greatly reduced trabecular BMD in the metaphysis of the distal femur (GX -44% and OVX -55%). Alendronate increased the trabecular BMD by 44% in GX rats and by 64% in OVX rats, while PTH increased it by 51% and 115%, respectively. However, estrogen increased the trabecular BMD in GX rats (35%), but not in OVX rats (15%, not significant). Cortical bone parameters were adversely (but moderately) affected by GX, but not by OVX or by treatment with the three drugs. INTERPRETATION: Alendronate, estrogen and PTH restored the trabecular bone loss in rats with an established GX-evoked osteopenia. In contrast, alendronate and PTH, but not estrogen, restored the trabecular bone loss after OVX. Hence, the mechanism underlying GX-evoked bone loss differs from that underlying OVX-evoked bone loss. The ability of alendronate, estrogen and PTH to reverse the GX-evoked osteopenia in the rat may be of clinical interest when dealing with bone loss in humans after GX.
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| 9. |
- Axelson, Jan, et al.
(författare)
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Importance of the stomach in maintaining calcium homeostatis in the rat
- 1991
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 32:11, s. 1298-1302
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Tidskriftsartikel (refereegranskat)abstract
- The stomach helps to maintain calcium homoeostasis by making dietary calcium accessible for uptake in the intestines, although the effect of the stomach on calcium homoeostasis is poorly understood. We examined the effect on blood calcium of gastric surgery in the rat. Within three weeks gastrectomy and fundectomy (excision of the acid producing part of the stomach) induced a slight lowering of the blood calcium concentration. When parathyroidectomy was combined with either gastrectomy or fundectomy the blood calcium concentrations promptly dropped to values lower than after parathyroidectomy alone. The mortality was close to 100% during the first three weeks after combined parathyroidectomy and gastric surgery. It was nil in rats subjected to parathyroidectomy alone. Gastrectomised rats absorbed Ca2+ better than unoperated control rats, possibly reflecting the fact that the serum 1,25-dihydroxyvitamin D concentration was raised. Gastrectomised rats had a food intake that was about 70% of that in intact rats, and the amount of dietary calcium absorbed (net absorption per kg body weight) by the gastrectomised rats was approximately 65% of that in intact control rats. We conclude that the acid producing part of the stomach is important for calcium homoeostasis, since its removal induced lethal hypocalcaemia in parathyroidectomised rats. One possible explanation for the hypocalcaemia induced by gastrectomy is a progressive calcium deficit. In addition, the loss of calciotrophic hormones originating in the stomach may contribute.
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| 10. |
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