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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrin-immunoreactive cells were fairly numerous in the pancreas and upper duodenum of the rat at about the time of birth. A minor population of these cells stained with antibodies directed against the N-terminal region of gastrin-34 as well as with antibodies directed against the C-terminal region. The remainder of the cells stained with the C-terminally directed antibodies only. Within a fortnight after birth all gastrin-immunoreactive cells disappeared from the pancreas and were greatly reduced in number in the duodenum; those that remained were probably CCK cells. Gastrin cells were rare in the antrum at birth and remained rare during the first days after birth. They increased in number, slowly until after weaning (15-20 days of age) and then more rapidly, until 25-30 days of age when the gastrin cell density reached that in adult rats. At the time of birth the gastrin concentration in serum was low; the subsequent increase during the first 2 weeks paralleled the development of the antral gastrin cell system. Adult postprandial serum gastrin concentrations were reached 12 days after birth. Somatostatin cells were rare in both the antral and oxyntic mucosa at birth. They increased gradually in number until about a month after birth when the cell density reached that seen in adult rats. In the oxyntic mucosa the ECL and A-like cells are the predominant endocrine (argyrophil) cell types. They were not detected until about 4 days after birth. Their number increased slowly until about 30 days of age. They did not stain argyrophil until about 2-4 weeks after birth. Parietal cells were few at birth; ultrastructurally they appeared to be in an active state and histochemically they were shown to contain carbonic anhydrase. The pH of the gastric content of newborn rats was close to 5; 15-17 days after birth the pH was about 4 in freely fed rats. In fasted rats shortly after birth the pH was about 4. Two weeks later it was around 2, which is the pH measured in older rats. Hence, the full capacity for acid secretion is probably not established until weaning. Fasting greatly lowers the serum gastrin concentration and the histidine decarboxylase activity of the ECL cells in adult rats. Before weaning, fasting produced these effects only to a minor degree.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine cells and parietal cells in the stomach of the developing rat. 286 80

In intact rats plasma gastrin levels were increased during a 20-wk treatment course with either omeprazole or ranitidine. Although plasma gastrin levels were the same during treatment, the enterochromaffinlike (ECL) cell density increased approximately linearly with time at a rate correlated to the plasma gastrin level. Antrectomy prevented the ECL cell hyperplasia seen in omeprazole-treated rats, suggesting that it was not caused by omeprazole per se. Changes in ECL cell density roughly paralleled changes in oxyntic mucosal histidine carboxylase activity and histamine concentration. Treatment with omeprazole also raised stomach weight and antral gastrin and gastrin cell density, reduced antral somatostatin cell density, but did not affect enterochromaffin cell density. Within 19 days of cessation of a 10-wk treatment course, plasma gastrin levels, oxyntic mucosal histidine decarboxylase activity, and antral gastrin and somatostatin cell densities had returned to control levels. The stomach weight was normal within 5-10 wk, antral gastrin concentration within 10 wk, and oxyntic mucosal ECL cell density and histamine concentration within 20 wk. After renewed treatment with omeprazole for 10 wk starting 10 wk after completion of the first omeprazole treatment period, changes in all parameters were of similar magnitude in animals previously treated with omeprazole and those previously treated with vehicle. The results suggest that the effects described are reversible and that gastrin cells turn over more rapidly than ECL cells.
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PMID:Time-course of development and reversal of gastric endocrine cell hyperplasia after inhibition of acid secretion. Studies with omeprazole and ranitidine in intact and antrectomized rats. 318 74

Changes in basal- and pentagastrin-stimulated gastric acid, pepsin secretion as well as gastric mucosal histidine decarboxylase activity were examined in 4- to 21-month-old pyloric ligated Fischer-344 rats. In addition, serum gastrin levels, gastric mucosal DNA, and RNA content were determined in these rats. The results revealed that whereas acid secretion decreased progressively with age, pepsin output increased between 4 and 14 months of age and then decreased sharply. Serum gastrin levels decreased progressively with age, and 3 h of pyloric obstruction produced no apparent change in serum gastrin levels in any of the age groups. Gastric mucosal weight, DNA, and RNA content in 4-month-old rats were not significantly different from those of 14-month-old animals. However, in 21-month-old rats, each of these values were found to be significantly lower than in their 4- or 14-month-old counterparts. A single injection of pentagastrin (250 micrograms/kg) significantly stimulated acid and pepsin secretion (45-52%) in 4-month-old rats, but not in 14- and 21-month-old animals, when compared with the corresponding saline-injected controls. Gastric mucosal histidine decarboxylase activity increased steadily between 4 and 21 months of age. Pentagastrin caused a significant 78% stimulation in histidine decarboxylase activity in 4-month-old rats, but had no effect on the enzyme activity in 14-month-old animals, when compared with the corresponding saline-injected controls. However, in 21-month-old rats, pentagastrin inhibited histidine decarboxylase activity by 55% when compared with the saline-injected controls. It is concluded that a) aging decreases capacity of the gastric mucosa to secrete acid and pepsin, b) in aged rats, decreased acid and pepsin output could in part be attributed to mucosal atrophy; c) responsiveness of the gastric mucosa to pentagastrin decreases with age; and d) in aged animals, gastric acid secretion is not regulated by histamine.
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PMID:Gastric secretion during aging in pyloric-ligated rats and effects of pentagastrin. 325 Aug 83

The gastric mucosal histamine level in mice increased by about 80% and 100% after fasting for 24 and 48 h, respectively. In non-fasted mice, alpha-fluoromethylhistidine (alpha-FMH), a specific histidine decarboxylase inhibitor, significantly decreased the histamine level, the reduction amounting to 35% and 49%, 2 h and 4 h after treatment, respectively. In mice fasted for 24 h, a significant decrease of 42% was observed 4 h after treatment. However, in mice fasted for 48 h, no significant decrease was seen even 4 h after alpha-FMH treatment. Therefore, the histamine-releasing effect of re-feeding and drugs on the gastric mucosa was examined in vivo, using animals fasted for 48 h and subsequently treated with alpha-FMH. Food given simultaneously with alpha-FMH to 48-h fasted mice significantly decreased the histamine level 4 h later. Pentagastrin and carbachol administered alone (0.25-2.0 mg/kg, i.p.) had no significant effect on the histamine level. However, the combined treatment with these drugs significantly decreased the histamine level. In rats fasted for 48 h and treated with alpha-FMH, pentagastrin (0.25 and 0.5 mg/kg, i.p.) but not carbachol (0.125-0.5 mg/kg, i.p.) caused a significant decrease in the mucosal histamine level. In contrast to mice, the effect of the combined treatment with pentagastrin and carbachol was not synergistic in rats. These findings suggest that gastrin acts synergistically with acetylcholine in the histamine release from the gastric mucosa in mice, whereas such synergism may not occur in rats.
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PMID:Effects of pentagastrin and carbachol on the gastric histamine level in alpha-fluoromethylhistidine-treated mice and rats. 343 95

Female rats were subjected to various treatments for 10 weeks to study effects on plasma gastrin levels. Intact rats were treated orally with omeprazole, 10 or 400 mumol/kg, ranitidine, 175 + 175 + 350 mumol/kg, or vehicle; antrectomized rats were treated with omeprazole, 400 mumol/kg, or vehicle. In addition to plasma gastrin levels, histidine decarboxylase (HDC) activity, histamine levels and ECL cell density in the oxyntic mucosa were determined. Gastrin levels were increased in unoperated rats treated with the high omeprazole dose and with ranitidine, whereas they were lowered in antrectomized controls. A small increase in plasma gastrin was seen in the low-dose omeprazole group. In antrectomized rats treated with omeprazole, the plasma gastrin level was the same as in intact control rats. The ECL cell density, the activity of HDC and the concentration of histamine in the oxyntic mucosa were found to reflect the plasma gastrin concentration. The results suggest that the changes in ECL cell density are secondary to the changes in plasma gastrin, induced by inhibition of acid secretion or antrectomy. It is concluded that neither omeprazole nor ranitidine per se is likely to induce proliferation of ECL cells.
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PMID:Inhibition of gastric acid secretion by omeprazole and ranitidine. Effects on plasma gastrin and gastric histamine, histidine decarboxylase activity and ECL cell density in normal and antrectomized rats. 346 Jan 71

Unoperated female rats were subjected to daily oral treatment with omeprazole (10 or 400 mumol/kg body wt), ranitidine (175 + 175 + 350 mumol/kg body wt), or vehicle and antrectomized rats were treated with omeprazole (400 mumol/kg body wt) or vehicle. After 10 wk of treatment, plasma gastrin levels were high in unoperated rats treated with the high omeprazole dose and with ranitidine, and low in antrectomized controls. Plasma gastrin levels were slightly higher in the low-dose omeprazole group than in the intact controls. In antrectomized rats treated with the high dose of omeprazole, the plasma gastrin level was in the same range as in intact control rats. A close correlation (r = 0.89, p less than 0.0001) was found between the plasma gastrin level and the oxyntic mucosal enterochromaffinlike cell density (as well as the tissue levels of histidine decarboxylase and histamine in the oxyntic mucosa) in all groups. The somatostatin cell density in the oxyntic mucosa was not altered by the various treatments. During a recovery period of 10 wk after the 10-wk treatment, the enterochromaffinlike cell density and histamine concentration decreased by 30%-40% in the rats treated with the high dose of omeprazole, whereas the corresponding values increased by 50% and 40%, respectively, in the control rats. The difference between the two groups, however, was still statistically significant. Plasma gastrin levels and gastric histidine decarboxylase activity returned to control values during recovery. The results suggest that the observed changes in enterochromaffinlike cell density are related to the plasma gastrin levels and that they are reversible. it is concluded that neither omeprazole nor ranitidine per se is likely to induce proliferation of enterochromaffinlike cells.
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PMID:Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats. 351 Jan 44

The stomach is rich in endocrine cells, most of which are still unidentified with respect to the peptide hormones they produce. The endocrine cell populations in the antrum usually differ from those in the oxyntic mucosa. Gastrin cells are found in the antrum and respond readily to stimuli from the gastric lumen, such as changes in the pH and the presence of food. In order to study the functional control of the antral gastrin cell, rats were subjected to different kinds of surgery. The serum gastrin concentrations in the various experimental groups were measured 8-10 weeks after the operations. Elevated antral pH raised the serum gastrin concentration. The combination of elevated antral pH and the passage of food over the pyloric glands produced gastrin cell hyperplasia. The operation that was most effective in inducing gastrin cell hyperplasia was removal of the acid-producing part of the stomach. Interestingly, gastrin cell hyperplasia was seen also after bilateral truncal vagotomy, indicating that an intact vagal innervation is not essential for the development of gastrin cell hyperplasia. Enterochromaffin-like (ECL) cells are endocrine/paracrine cells that are numerous in the acid-producing part of the stomach in many species. In the rat, they occur predominantly in the basal half of the oxyntic mucosa and produce and store histamine. The ECL cells have an unknown function and do not seem to respond to stimuli from the gastric lumen. They are activated by circulating gastrin and by vagal excitation. Gastrin mobilises histamine from these cells and activates the histamine-forming enzyme, histidine decarboxylase. Long-term hypergastrinaemia produces diffuse ECL cell hyperplasia, whereas hypogastrinaemia (following removal of the endogenous stores of gastrin by antrectomy) reduces the ECL cell number. Portacaval shunt brings about a marked increase in the number of ECL cells through an unknown mechanism. Also neuronal stimuli are important for the trophic control of the ECL cells. Studies of unilaterally vagotomised rats showed reduced weight and thickness of the oxyntic mucosa as well as a markedly reduced number of ECL cells on the denervated side. Gastric carcinoids in man are rare tumours predominantly made up of ECL cells. The incidence of such tumours is increased in patients with hypergastrinaemia (pernicious anaemia, Zollinger-Ellison syndrome). A diffuse ECL cell hyperplasia is a common finding in such patients, which is in keeping with the known gastrin sensitivity of the normal ECL cell in the rat.
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PMID:Activation and hyperplasia of gastrin and enterochromaffin-like cells in the stomach. 353 78

The availability of potent and long-acting blockers of acid secretion, such as omeprazole, has paved the way for experimental studies on the long-term effects of permanently raised levels of circulating gastrin without the complication of surgical intervention. We have examined rats given high doses of the antisecretagogues omeprazole and ranitidine during 10 or 20 weeks for general trophic effects on the gastrointestinal tract and pancreas and for the effects on endocrine cells such as the somatostatin cells and the enterochromaffin-like (ECL) cells, which are present in the oxyntic mucosa. The ECL cells, which in the rat produce and store histamine (in addition to an as yet unidentified peptide hormone), are known to be activated by gastrin. In rats given high doses of omeprazole, the serum gastrin levels rose about 10-fold. General trophic effects were restricted to the stomach; the weight was increased, as was the thickness of the oxyntic mucosa. Omeprazole treatment resulted in a 3- to 5-fold increase in the ECL cell density. A close correlation was found between plasma gastrin levels and the ECL cell density as well as the levels of histidine decarboxylase and histamine in the oxyntic mucosa. The somatostatin cell density was unaffected by the hypergastrinemia. During a 10-week recovery period after discontinuation of the omeprazole treatment, the ECL cell density diminished, but was still significantly higher than in age-matched control rats. Plasma gastrin levels and gastric histidine decarboxylase activity rapidly returned to control values. The results suggest that the observed general trophic effects on the oxyntic mucosa and on the ECL cells are related to the plasma gastrin levels and not to an action of the antisecretagogues per se.
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PMID:Hypergastrinemia after blockade of acid secretion in the rat: trophic effects. 379 72

In portacaval-shunted rats, basal but not pentagastrin-stimulated acid secretion was higher than in sham-operated controls. The basal serum gastrin concentration was unchanged and the postprandial serum gastrin concentration lowered following portacaval shunt. Thus, gastrin is not responsible for the elevated basal acid secretion. The present study provides evidence that there is no trophic effect on the oxyntic mucosa as a whole and that there is no change in parietal cell-associated gastrin receptors after portacaval shunting. Interestingly, however, endocrine cells in the oxyntic mucosa (the histamine-containing ECL cells) proliferated greatly and the pentagastrin- and cholecystokinin octapeptide-induced activation of the histamine-forming enzyme, histidine decarboxylase, in these cells was much greater than in control rats. Analysis of the dose-response curves for the enzyme-activating effect of pentagastrin and cholecystokinin-octapeptide indicated that the D50 values for these two stimulants were not altered by shunting but that the maximal enzyme activation was greatly elevated. The enhanced enzyme activation can be partly, but not fully, explained by the fact that the ECL cells were increased in number. The enhanced response following portacaval shunt probably reflects also an increased number of gastrin receptors per ECL cell. The effect of portacaval shunting on gastric ECL cells can perhaps be explained by impaired degradation in the liver of intestinal substance(s) exerting a highly specific trophic effect on the ECL cells or, alternatively, causing an enrichment of gastrin receptors on these cells, thereby making them more sensitive to the trophic effect of gastrin. The ECL cell hyperplasia is manifest about 4 weeks after the shunting. A modified procedure for portacaval shunting which left the gastroduodenal vein (otherwise ligated) drained to the liver produced the same trophic effect as conventional portacaval shunt, suggesting an intestinal rather than gastroduodenal origin of the agent(s) responsible for the trophic action.
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PMID:Effects of portacaval shunt on the rat stomach. 405 Apr 76

Bilateral nephrectomy in the rat is followed by hypergastrinaemia and by activation of gastric histidine decarboxylase. The enzyme activity is thought to reflect the concentration of circulating gastrin. While there is general agreement that post-nephrectomy hypergastrinaemia is primarily the result of loss of renal elimination of gastrin, it remained to be determined whether gastrin secretion could be stimulated in the hypergastrinaemic state and whether it contributed to the hypergastrinaemia. Histamine, but not pentagastrin, is known to evoke gastric acid secretion in the nephrectomized rat, and histamine, but not pentagastrin, was found to lower the serum gastrin level and the gastric histidine decarboxylase activity, indicating that after nephrectomy gastrin was still secreted and that the secretion could be suppressed by increased acid output. The importance of gastrin secretion for post-nephrectomy hypergastrinaemia was assessed further by investigating the effect of nephrectomy on the serum gastrin concentration in rats previously subjected to operations that had either reduced (e.g. antrectomy) or raised (e.g. antrum exclusion) the serum gastrin concentration. Post-nephrectomy serum gastrin levels co-varied with the levels before nephrectomy. Thus, the capacity to secrete gastrin was not abolished by nephrectomy. Finally, nephrectomy greatly affected the linear correlation between the serum gastrin concentration and the gastric histidine decarboxylase activity in a manner suggesting the operation of a gastrin-independent factor capable of activating the enzyme.
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PMID:Mechanism of hypergastrinaemia after nephrectomy in the rat. 408 43


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