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- Gagnemo Persson, Rebecca, et al.
(författare)
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Chicken parathyroid hormone gene expression in response to gastrin, omeprazole, ergocalciferol, and restricted food intake.
- 1997
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Ingår i: Calcified Tissue International. - 1432-0827. ; 61:3, s. 210-215
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens, omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting blood calcium. The first part of the present study was concerned with the effect of omeprazole, ergocalciferol (vitamin D2), and restricted food intake on the gene expression of parathyroid hormone (PTH) in the parathyroid glands of the chicken. Chickens were treated with omeprazole (400 micromol/kg/day, I.M.), food restriction, omeprazole + food restriction, ergocalciferol (250 000 IU/kg/day, S.C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of the chickens was monitored, and the weights of the parathyroid glands and femurs were determined at sacrifice. PTH mRNA in the parathyroid glands was analyzed by Northern blot. The second part of the study examined the effect of 3 weeks of continuous gastrin infusion (chicken gastrin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression. Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were without effect, but food restriction greatly enhanced the omeprazole-evoked increase in parathyroid gland weight and PTH gene expression. Gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.
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| 2. |
- Gagnemo Persson, Rebecca, et al.
(författare)
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Rat stomach ECL-cell histidine decarboxylase activity is suppressed by ergocalciferol but unaffected by parathyroid hormone and calcitonin.
- 1999
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Ingår i: Regulatory Peptides. - 1873-1686. ; 79:2-3, s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- The ECL cells are peptide hormone-producing cells, rich in histamine and chromogranin A (CGA)-derived peptides, that operate under the control of gastrin. Gastrin and the ECL cells form a functional unit, the gastrin-ECL-cell axis. The aims of the present study were to examine (1) if calcitonin (CT), parathyroid hormone (PTH) and vitamin D affect the gastrin-ECL-cell axis (by measuring the activity of the histamine-forming enzyme, histidine decarboxylase (HDC), and the expression of HDC mRNA and CGA mRNA in the ECL cells), and (2) if activation of the gastrin-ECL-cell axis affects the parathyroid glands (by measuring plasma PTH and mRNA expression). We also examined the possibility that the oxyntic mucosa harbours vitamin D receptors. Fasted rats received intravenous infusion of PTH and CT with or without gastrin. PTH raised the blood Ca2+ concentration, whereas CT infusion lowered it. Plasma PTH rose in response to CT, while serum gastrin remained unaffected. ECL-cell HDC was activated by gastrin but not by CT and PTH. Five daily subcutaneous injections of large amounts of ergocalciferol raised the blood Ca2+ concentration, while reducing the oxyntic mucosal HDC activity and the expression of HDC and CGA mRNA. The serum gastrin concentration was not affected. The findings are in line with the idea that the gastrin-ECL-cell axis can be suppressed by vitamin D or by vitamin D-dependent mechanisms. Western blot analysis revealed the presence of vitamin D receptor immunoreactivity and reverse transcription PCR detected vitamin D receptor gene expression in the rat oxyntic mucosa. Hypergastrinemia was induced by daily peroral treatment with the H+/K+-ATPase inhibitor, omeprazole, for 2 weeks or by continuous subcutaneous infusion of gastrin for 7 days. Elevated serum gastrin concentration was associated with increased HDC activity and increased HDC and CGA mRNA expression in the oxyntic mucosa. There was no elevation of plasma PTH or PTH mRNA expression in the parathyroid gland.
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| 3. |
- Gagnemo Persson, Rebecca
(författare)
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Interaction between Calcium, Calciotropic Hormones and the Gastrin-ECL-cell Axis
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Calcium homeostasis involves mainly the interaction of PTH, vitamin D and CT. The stomach may be important for calcium homeostasis. Gastric acid is thought to mobilize calcium from the diet, thereby facilitating the absorption of calcium in the small intestines. In the rat, gastrectomy rapidly reduces the calcium content, the density and the trabecular volume of the bone. The gastrectomy-evoked bone loss cannot be prevented by supplementation with CaCl2 and it is unlikely to reflect either calcium or vitamin D deficiency. It may reflect the lack of a calciotropic or osteotropic hormone, that emanates from the oxyntic mucosa. Gastrin has been suggested to release a hypocalcemic peptide hormone, gastrocalcin, from the oxyntic mucosal ECL cells, which is thought to act to enhance the uptake of Ca into bone. Gastrin has also been suggested to have a growth-promoting effect on the parathyroid gland. The present study examines the possibility that the gastrin-ECL-cell axis is integrated with known regulatory systems for calcium and bone metabolism. Omeprazole treatment, which activates the gastrin-ECL-cell axis, was associated with hypertrophy and hyperplasia of the chicken parathyroid glands. Dietary calcium seems to enhance the release of gastrin without activating the ECL cells of the rat stomach. Acute perturbations in circulating calcium did not affect either the release of gastrin or the activity of the ECL cells in the rat. Short-term administration of PTH or CT had no effect on the serum gastrin concentration or on the activity of the ECL cells. Vitamin D suppressed the activity of the ECL cells, presumably via vitamin D receptors in the oxyntic mucosa.The gastrin-ECL-cell axis appears to be functionally integrated with vitamin D-dependent and PTH-dependent regulatory systems and may play a role in bone metabolism.
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| 4. |
- Håkanson, Rolf, et al.
(författare)
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Perturbations in blood Ca2+ do not affect the activity of rat stomach enterochromaffin-like cells.
- 1996
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Ingår i: Scandinavian Journal of Gastroenterology. - 1502-7708. ; 31:3, s. 217-221
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrin stimulates uptake of Ca(2)+ into bone and causes transient hypocalcemia, possibly by releasing a peptide hormone from enterochromaffin-like (ECL) cells, which are histamine- and peptidehormone-producing cells in the acid-producing part of the stomach. However, if ECL cells secrete a calciotropic hormone, it is to be expected that their activity is affected by the serum Ca(2)+ concentration.METHODS: Food-deprived male rats were infused with human (Leu)15-gastrin-17 and/or ethylenediamine-tetraacetic acid and CaCl(2). The blood Ca(2)+ level was monitored throughout the experiments (3 h), and the serum concentrations of gastrin, parathyroid hormone, and calcitonin were measured at death. The activity of the ECL cells was assessed by measuring the histidine decarboxylase (HDC) activity.RESULTS: Gastrin produced the expected increase in HDC activity, but neither hyper- nor hypo-calcemia affected the RDC activity of either hypo- or hyper-gastrinemic rats.CONCLUSION: Perturbations in blood Ca(2)+ do not seem to affect ECL cells, which is at odds with the view that ECL cells harbor a calciotropic hormone.
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