Rebecca Gagnemo Persson - Academia.edu (original) (raw)

Papers by Rebecca Gagnemo Persson

Scandinavian Journal of Gastroenterology, 1996

Gastrin stimulates uptake of Ca(2)+ into bone and causes transient hypocalcemia, possibly by rele... more 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. 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. 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. 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.

Endocrinology, 1991

As in the rat, gastrin and an extract of the acid-producing part of the stomach (proventriculus) ... more As in the rat, gastrin and an extract of the acid-producing part of the stomach (proventriculus) were found to lower the blood Ca2+ concentration in the chicken. Furthermore, gastrin enhanced the uptake of 45Ca into the femur. It has been suggested previously that gastrin causes hypocalcemia in the rat by releasing gastrocalcin, a hypothetical hormone thought to reside in the acid-producing part of the stomach. The results of the present study in the chicken are in agreement with this concept. Not only exogenous, but also endogenous gastrin lowered blood calcium levels. Thus, the serum gastrin concentration was increased in response to ranitidine-evoked blockade of the gastric acid output; the rise in gastrin was associated with a transient drop in blood calcium. Also, food intake produced a rise in the serum gastrin concentration and a transient drop in blood calcium. However, injection of ranitidine or food intake in proventriclectomized (acid-producing part of the stomach extirpated) chickens failed to lower blood calcium, supporting the view that the gastrin-evoked hypocalcemia depends upon an agent in the gastric (proventriculus) mucosa. We suggest that endogenous and exogenous gastrin evoke hypocalcemia in the chicken by the same mechanism as that which has been postulated in the rat, i.e. by mobilization of the candidate hormone gastrocalcin from endocrine cells in the acid-producing gastric mucosa.

Calcified Tissue International, 1997

Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hyperga... more 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 μmol/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.

Regulatory Peptides, 2002

Histamine-producing ECL cells and ghrelin-producing A-like cells are endocrine/paracrine cell pop... more Histamine-producing ECL cells and ghrelin-producing A-like cells are endocrine/paracrine cell populations in the acid-producing part of the rat stomach. While the A-like cells operate independently of gastrin, the ECL cells respond to gastrin with mobilization of histamine and chromogranin A (CGA)-derived peptides, such as pancreastatin. Gastrin is often assumed to be the driving force behind the postnatal development of the gastric mucosa in general and the ECL cells in particular. We tested this assumption by examining the oxyntic mucosa (with ECL cells and A-like cells) in developing rats under the influence of YF476, a cholecystokinin-2 (CCK 2 ) receptor antagonist. The drug was administered by weekly subcutaneous injections starting at birth. The body weight gain was not affected. Weaning occurred at days 15 -22 in both YF476-treated and age-matched control rats. Circulating gastrin was low at birth and reached adult levels 2 weeks after birth. During and after weaning (but not before), YF476 greatly raised the serum gastrin concentration (because of abolished acid feedback inhibition of gastrin release). The weight of the stomach was unaffected by YF476 during the first 2 -3 weeks after birth. From 4 to 5 weeks of age, the weight and thickness of the gastric mucosa were lower in YF476-treated rats than in controls. Pancreastatin-immunoreactive cells (i.e. all endocrine cells in the stomach) and ghrelin-immunoreactive cells (A-like cells) were few at birth and increased gradually in number until 6 -8 weeks of age (control rats). At first, YF476 did not affect the development of the pancreastatin-immunoreactive cells, but a few weeks after weaning, the cells were fewer in the YF476 rats. The ECL-cell parameters (oxyntic mucosal histamine and pancreastatin concentrations, the histidine decarboxylase (HDC) activity, the HDC mRNA levels and serum pancreastatin concentration) increased slowly until weaning in both YF476-treated and control rats. From then on, there was a further increase in the ECL-cell parameters in control rats but not in YF476 rats. The postnatal development of the ghrelin cells (i.e. the A-like cells) and of the A-like cell parameters (the oxyntic mucosal ghrelin concentration and the serum ghrelin concentrations) was not affected by YF476 at any point.

Biochemical and Biophysical Research Communications, 2000

Proteinase-activated receptors (PARs) are activated by proteolytic removal of a short amino termi... more Proteinase-activated receptors (PARs) are activated by proteolytic removal of a short amino terminal peptide, thus exposing a new amino terminus that functions as a tethered ligand that activates the receptor. With the aim to identify and study potential activators of PAR-2 we have developed a new method to measure proteolytic cleavage of PARs. PAR-2 was tagged with the insulin C-peptide that upon receptor cleavage is released and quantified using an ELISA. The modified receptor, shown to be functional in mouse 3T3 cells, was expressed in an insect cell line and the ability of different proteinases to cleave PAR-2 was studied. Two different mast cell tryptases cleaved PAR-2 in a concentration dependent manner, but were much less potent than pancreatic trypsin and trypsin-2 isolated from a carcinoma cell line. Pancreatic trypsin and trypsin-2 were almost equally effective at cleaving PAR-2 suggesting that extrapancreatic trypsins are potential in vivo activators of PAR-2.

Scandinavian Journal of Gastroenterology, 1994

Omeprazole, a long-acting inhibitor of gastric acid secretion, is able to increase the circulatin... more Omeprazole, a long-acting inhibitor of gastric acid secretion, is able to increase the circulating concentrations of gastrin. Daily treatment with high doses of omeprazole cause sustained hypergastrinemia. Long-standing hypergastrinemia can be expected to exert numerous effects in the body. For instance, gastrin has been proposed to promote growth in the digestive tract and pancreas. The present study is concerned with the effect of omeprazole on parathyroid glands in the chicken. Chickens were treated with omeprazole (400 mumol/kg/day) in methylcellulose (2.5 ml/kg) for 5 or 10 weeks. Controls received vehicle. Blood calcium and serum gastrin concentrations were studied. The weight gain of the animals and of various organs (proventriculus, antrum, thyroids, parathyroids, ultimobranchial glands, and femur) were determined. The DNA content and the size of the parathyroid chief cells were also determined. Omeprazole reduced the body weight gain while greatly increasing the weight of the proventriculus and the parathyroid glands. The weight and density of the femur were reduced. The circulating concentrations of calcium were unaffected. The DNA content of the parathyroid glands was increased, and morphometric analysis of the parathyroid chief cells showed an increased cell size. Thus, the increased parathyroid gland weight seems to reflect both hypertrophy and hyperplasia. There was a slight increase in the weight of the ultimobranchial glands (expressed per kilogram body weight). The weight of the thyroids was unaffected (expressed in relation to body weight). The results indicate that omeprazole treatment in chickens leads not only to trophic effects in the acid-producing gastric mucosa (probably because of the ensuing hypergastrinemia), as reported earlier, but also to growth of the parathyroid glands (both hypertrophy and hyperplasia) and to bone loss without affecting blood calcium values. The mechanism behind these effects remains unknown.

Pharmacology & Toxicology, 2001

Gastrin has a growth-promoting effect on the oxyntic mucosa of the stomach but has been claimed a... more Gastrin has a growth-promoting effect on the oxyntic mucosa of the stomach but has been claimed also to affect other parts of the gastrointestinal tract and pancreas. This report describes the effects of the cholecystokinin 2 (CCK 2 ) receptor antagonists YM022 and YF476 on various growth parameters in the gastrointestinal tract and pancreas of the rat. YM022 and YF476 were given subcutaneously in doses known to produce maximum and sustained CCK 2 receptor blockade. The body weight was not affected. However, the oxyntic mucosal weight, thickness and protein and DNA contents were reduced by 15-20% already within 1-2 days and by about 30% after 4-8 weeks of CCK 2 receptor blockade. Hence, the response of the oxyntic mucosa to CCK 2 receptor blockade was in the form of hypotrophy (reduced protein content) and hypoplasia (reduced DNA content). There were no obvious effects of CCK 2 receptor blockade on the intestine or pancreas (nor on liver, kidney or thyroid). The proton pump inhibitor omeprazole was used to induce hypergastrinaemia and was given with or without YM022. Omeprazole treatment for 4 weeks increased the oxyntic mucosal weight and thickness by 15-20%. YM022 prevented these effects. We conclude that while elevated circulating gastrin levels, acting on CCK 2 receptors, exert a growth-promoting effect on the oxyntic mucosa (but not elsewhere), normal serum gastrin levels exert a mucosa-preserving effect.

Gut, 1991

The stomach helps to maintain calcium homoeostasis by making dietary calcium accessible for uptak... more 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 ofgastric surgery in the rat. Within three weeks gastrectomy and fundectomy (excision of the acid producing part ofthe stomach) induced a slight lowering of the blood calcium concentration.

Calcified Tissue International, 1993

Young male rats (100 g body weight) were fed diets containing varying amounts of calcium. Body we... more Young male rats (100 g body weight) were fed diets containing varying amounts of calcium. Body weight and bone development were studied together with various endocrine parameters, including blood levels of Ca2+, calcitonin, parathyroid hormone, vitamin D, and gastrin, and the enterochromaffin-like (ECL) cell-related parameters gastric mucosal histidine decarboxylase activity and histamine concentration. A diet containing 0.5% calcium resulted in ontimum body weight gain and bone development. A lower calcium intake impaired body weight gain and bone development. The impairment was manifested in reduced bone calcium content whereas the size of the bones was unaffected. The net absorption of calcium seemed to be proportional to the calcium intake. A low calcium diet (0.03%) raised the circulating levels of 1,25(OH)2D and parathyroid hormone and lowered 25(OH)D3 and Ca2+, whereas a high calcium diet (5.46%) raised calcitonin, Ca2+, 25(OH)D3, and 1,25(OH)2D. In addition, the low calcium diet lowered the circulating gastrin concentation and the histidine decarboxylase activity and histamine content of the ECL cells in the gastric mucosa. A high calcium diet raised the circulating gastrin concentration, but the rise was not associated with an increase in the histidine decarboxylase activity and histamine content.

Regulatory Peptides, 1999