Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine tumours (argyrophil cell carcinoids) are frequent in the oxyntic mucosa of mastomys. The tumour is notable for its high histamine content and for its high histidine decarboxylase activity. The tumour is thought to arise from the histamine-storing, enterochromaffin-like cells of the oxyntic mucosa. They are of two ultrastructurally distinguishable types, ECL cells and A-like cells, both of which have been demonstrated in the tumour. Identical cells have been demonstrated in the oxyntic mucosa of the rat; there is much evidence that in this species the functional activity and the number of these cells are determined by the serum gastrin concentration. However, tumours have never been found to arise from these cells in the rat. As an initial step in an attempt to explain the formation of the gastric endocrine tumour in the mastomys we examined the distribution and frequency of occurrence of endocrine cells in the mastomys stomach. Gastrin cells in the antrum of mastomys seemed to occur in about the same frequency as in the antrum of rat and mouse. 5-HT-storing enterochromaffin cells, however, were considerably more numerous in the mastomys, whereas the somatostatin cells in the antrum were fewer. The number of enterochromaffin-like cells and somatostratin cells in the oxyntic mucosa of mastomys was much lower than in the rat and mouse. Once developed, the gastric endocrine tumour seems to reduce the antral gastrin cell number; the larger the tumour the greater the reduction.
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PMID:Spontaneous argyrophil cell carcinoid in the glandular stomach: immunohistochemical study of gastric endocrine cells in normal and tumour-bearing mastomys. 38 3

The enterochromaffin-like (ECL) cells represent the predominant endocrine cell population in the acid-producing part of the stomach of both experimental animals and man. These cells actively produce and store histamine in addition to an anticipated but as yet unidentified peptide hormone and are under the control of gastrin. An acute gastrin stimulus causes exocytosis of the cytoplasmic granules/vesicles (and release of histamine and activation of the histamine-forming enzyme, histidine decarboxylase), while a more sustained gastrin stimulus causes first hypertrophy and then hyperplasia of the ECL cells in the rat (at most, a fivefold increase in the cell number). These effects can be demonstrated following infusion of gastrin or following an increase in the concentration of circulating gastrin of endogenous origin. The growth of the ECL cells reflects an accelerated self-replication rate. As studied in the rat, the self-replication rate is accelerated quite soon after induction of hypergastrinemia (blockade of acid secretion), the rate is maximally elevated within two weeks and then declines to control values at ten and 20 weeks despite the sustained hypergastrinemia. Lifelong hypergastrinemia in rats is associated not only with ECL-cell hyperplasia but also with an increased incidence of ECL-cell carcinoids. Recently, we could show that alpha-fluoromethylhistidine, which is a suicide inhibitor of histidine decarboxylase, effectively depletes the ECL cells of histamine and that the histamine-depleted ECL cells respond to gastrin with hyperplasia in a manner identical to normal ECL cells. Other factors beside gastrin seem to participate in the control of ECL-cell function and proliferation. Although exogenous somatostatin is known to suppress the activity of the ECL cells, we have failed to obtain evidence that the somatostatin cells in the oxyntic mucosa play a role in the physiological control of the ECL cells. The vagus, however, is important for the ability of the ECL cells to respond to gastrin. This conclusion is based on the observation that vagal denervation suppresses the hyperplastic response of the ECL cells to gastrin. Porta-cava shunting, on the other hand, greatly enhances the responsiveness of the ECL cells to gastrin. The mechanism behind this effect is unknown.
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PMID:The biology and pathobiology of the ECL cells. 134 Oct 77

This study compares the effects of lansoprazole and omeprazole on the activation and proliferation of enterochromaffin-like (ECL) cells in the rat stomach. Lansoprazole was given orally once daily for 10 weeks in two doses, 135 and 200 mumol/kg. Omeprazole was given by the same regimen in a dose of 400 mumol/kg, which is equipotent in terms of acid inhibition to the higher lansoprazole dose. Lansoprazole (both doses) as well as omeprazole raised the plasma gastrin levels about 11-fold 2 h after dosing and 8-to 10-fold 24 h after dosing, reflecting complete (2 h) and 70-80% (24 h) reductions of gastric acid secretion. Administration of either drug for 10 weeks increased the weight of the stomach and the oxyntic mucosa. The oxyntic mucosal histidine decarboxylase activity, histamine concentration and ECL cell density were increased to the same extent in the rats given either of the two lansoprazole doses or omeprazole. The numbers of antral gastrin cells were doubled and the numbers of antral somatostatin cells half that in the controls. These results show that long-standing lansoprazole-evoked hypergastrinemia affects the ECL cell similarly to omeprazole, ranitidine and other acid secretion inhibitors.
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PMID:Lansoprazole and omeprazole have similar effects on plasma gastrin levels, enterochromaffin-like cells, gastrin cells and somatostatin cells in the rat stomach. 135 46

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

A bovine milk diet (BM) resulted in remarkable changes in histamine H2 receptor activity (sensitization) and PGE2 receptor activity (desensitization) in gastric glands isolated from adult rats. In contrast, the receptor-cAMP systems sensitive to glucagon(s) and secretin in parietal cells and muco-peptic cells were unaffected. In the two experimental groups, cimetidine produced a parallel displacement of the histamine dose-response curve suggesting competitive inhibition between this classical H2 receptor antagonist and histamine. The BM diet reduced the histidine decarboxylase activity in rat gastric mucosa; the histamine content was not significantly different in control and BM-fed rats. There was no alteration of the circadian rhythm of the parietal cell (ultrastructural changes: microvilli, tubulo-vesicles) determined at intervals of 6 hours in milk-fed rats. Prostaglandins and other components in milk (EGF, somatostatin, etc.) might therefore protect gastric mucosa by a differential control of PGE2 and histamine H2 receptor activity, either directly (PGE2 and EGF in milk) or indirectly (inhibition of endogeneous histamine synthesis/release and stimulation of prostaglandin synthesis/release).
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PMID:Effect of a milk diet on rat gastric mucosa: receptor activity, histamine metabolism and ultrastructural analyses. 303 66

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

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 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

Somatostatin is a potent inhibitor of gastric acid secretion. However, the effect of somatostatin on gastric histamine secretion and synthesis has not been well understood, despite the fact that histamine plays a key role in the regulation of gastric acid secretion. This study was designed to determine the effect of somatostatin on gastric histamine mobilization and acid secretion in conscious rats. In conscious rats with a gastric fistula, a 4 h intravenous infusion of gastrin-17 I (1 nmol/kg/h) evoked a marked increase in fundic histidine decarboxylase activity (the sole histamine-forming enzyme) and reduced fundic histamine content with a concomitant increase in gastric acid secretion. Somatostatin-14 (10 nmol/kg/h) significantly inhibited gastrin-induced gastric acid secretion and fundic histidine decarboxylase activity and prevented a gastrin-induced decrease in fundic histamine content. In conscious rats with a vesical fistula, somatostatin-14 (10 nmol/kg/h) significantly inhibited the urinary histamine excretion induced by a gastrin-17 I (1 nmol/kg/h) infusion. These findings suggest that the inhibitory action of somatostatin on gastrin-induced acid secretion is mediated by the inhibition of histamine mobilization.
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PMID:Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the rat. 750 34

The effect of octreotide, a potent and long-acting analogue of somatostatin, on gastrin-stimulated proliferation and function of enterochromaffin-like (ECL) cells were examined in rats. Animals were divided into four groups and each group was continuously infused with saline, octreotide alone (40 micrograms/kg per day), gastrin alone (60 nmol/kg per day), or octreotide (40 micrograms/kg per day) plus gastrin (60 nmol/kg per day) respectively for 9 days via osmotic minipumps. Gastrin induced the increase of the bromodeoxyuridine labeling index and density of oxyntic mucosal ECL cells as well as oxyntic mucosal histidine decarboxylase activity. Octreotide completely abolished the gastrin-induced increases in the labeling index and density of ECL cells and oxyntic mucosal histidine decarboxylase activity. These results indicate that octreotide inhibits gastrin-stimulated proliferation of ECL cells and histamine production by these cells.
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PMID:Inhibition of gastrin-stimulated enterochromaffin-like cell proliferation and mucosal histamine production in the rat stomach by the somatostatin analogue octreotide. 754 3


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