Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Omeprazole, a potent inhibitor of acid secretion, is effective in adults with severe gastroesophageal reflux, but no such data are available on children. We studied 15 children in whom treatment with histamine (type 2) blockers and prokinetic agents had failed; 4 had also had one or more fundoplications. Their ages were 0.8 to 17 years (mean, 8.1 years) and weights were 7.5 to 30.7 kg (mean, 18.6 kg). Of the 15 children, 8 were neurologically handicapped. All patients had endoscopic and histologic evidence of esophagitis; most had esophagitis grade 3 to 4. Patients were initially given omeprazole at 10 to 20 mg; the dose was titrated upward until results of a subsequent 24-hour intraesophageal pH study was normal. Symptoms and signs abated and evidence of esophagitis diminished in all patients. Omeprazole was given for periods of 5.5 to 26 months (mean, 12.2 months). The effective total dose was 20 to 40 mg (0.7 to 3.3 mg/kg) in 11 patients, 10 mg (0.7 mg/kg) in 1 patient, and 60 mg (1.9 to 2.4 mg/kg) in 3 patients. The dosage range was 0.7 to 3.3 to mg/kg per day (mean, 1.9 mg/kg). Mildly elevated transaminase values in 7 patients and elevated fasting gastrin levels in 11 patients were present; in 6 of the 11, gastrin levels were 3 to 5.5 times the upper limit of normal. We found omeprazole to be highly effective in this group of patients with severe esophagitis refractory to other measures. We recommend a starting dose of 0.7 mg/kg as a single morning dose; the adequacy of reflux control is then determined by follow-up 24-hour intraesophageal pH studies. Omeprazole appears to be safe for short-term use, but further studies are needed to assess long-term safety because the significance of chronically elevated gastrin levels in children is unknown.
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PMID:Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. 830 51

Omeprazole, a potent and long-acting inhibitor of gastric acid secretion, is known to increase both serum gastrin and pepsinogen A and C levels in unoperated subjects. It has been suggested that the rise in serum pepsinogens is mediated by the omeprazole-induced increase in serum gastrin. This study was undertaken to determine the role of gastrin in hyper-pepsinogenemia induced by antisecretory therapy. We have studied the effect of a 5-day course of 40 mg of omeprazole daily on fasting serum gastrin and pepsinogen A and C levels in 14 patients with an antrectomy and a Billroth I anastomosis (n = 8) or a Billroth II anastomosis (n = 6). In antrectomized patients omeprazole failed to induce any increase in basal serum gastrin. On the other hand, omeprazole increased significantly serum pepsinogen A levels in both Billroth I and II patients, while the rise in serum pepsinogen C level was significant in Billroth I, but just failed to reach statistical significance in Billroth II patients. We conclude that the stimulation of serum pepsinogens A and C by a short-term treatment with omeprazole is not mediated by increases in serum gastrin. This study further shows that omeprazole stimulates gastrin release only from the antrum and not from extra-antral sources.
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PMID:Effect of short-term administration of omeprazole on serum gastrin and pepsinogens in antrectomized patients. 835 54

Omeprazole may exert an effect on gastric mucosal proliferation by inhibiting gastric acid secretion and increasing serum gastrin levels. It may also influence the kinetics of endocrine cells and the oxyntic mucosa. The aim of the present study was to evaluate the cell cycle in different gastric compartments following short- (1 month) and long-term (6 months) administration of two different dosages of omeprazole by means of a flow cytometric method. We also determined serum gastrin levels at the same time. No differences in cell cycle distribution of the antrum, body, and fundus were found in the two different dosage groups after 1 month of therapy, considering the synthetic phase (S-phase) of the cell cycle. A statistically significant increase in S-phase was reported after long-term therapy in the mucosa of the fundus and body of the stomach in both groups. Gastrin levels showed no clear correlation with cell cycle distribution variables. We postulate a proliferative adaptation of the oxyntic mucosa to long-term drug administration not mediated by gastrin influence.
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PMID:Effect of short- and long-term treatment with omeprazole on cell cycle distribution in the gastric mucosa. Results of a flow cytometric study. 836 16

The experience received hitherto with the treatment of omeprazole proves this drug as absolutely save and poor of side effects. ECL-cell hyperplasia and carcinoids which occur during application of very high doses of omeprazole in rats are not caused by a direct effect of omeprazole. These changes are induced by extremely elevated serum gastrin levels due to achlorhydria. However, these high doses of omeprazole are not applicated in man. Therefore, the results from animal studies can not be applied on humans. During long-term treatment with omeprazole in most patients only slight increases of serum gastrin levels and ECL-cell densities occur. Only a very few patients exhibit a progressive and marked increase of serum gastrin levels. These patients should be carefully monitored by endoscopy in regularly intervals. There is no current evidence to support the contention that omeprazole is genotoxic. Results from Burlinson on the potential of omeprazole to induce DNA damage proved to be unsounded and of no clinical relevance. Omeprazole produced negative results in all well established genotoxicity tests. The incidence of neoplasias in the stomach is not increased after long-term acid suppression as indicated by 15 years application of H2-blockers and even a longer period of experience with vagotomy. Hitherto, there is also no evidence that acid inhibition induced by omeprazole causes an increased rate of carcinoma of the stomach. The risk for promoting carcinomas of the colon by the mild hypergastrinaemia during treatment with omeprazole seems to be inferior. In addition the correlation between development of carcinomas of the colon respective rectum and hypergastrinaemia is discussed controversly.
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PMID:[Risk for developing tumors in therapy with the proton pump inhibitor omeprazole]. 837 45

Whether the long acting somatostatin analogue SMS 201-995 (octreotide, Sandostatin) could inhibit the basal and meal stimulated hypergastrinaemia and hyperpepsinogenaemia induced by omeprazole was investigated. Eight healthy subjects were randomised to receive five day courses of SMS 201-995 (25 micrograms subcutaneously three times daily), omeprazole (40 mg once a day), a combination of both drugs, or placebo. Basal and meal stimulated serum gastrin and basal serum pepsinogen A and C values were measured the day before treatment, on day five of treatment, and the day after each course of treatment. Omeprazole caused significant increases in basal and meal stimulated peak and integrated serum gastrin values and pepsinogen A and C levels, which were still significantly raised the day after stopping omeprazole treatment. Giving SMS 201-995 with omeprazole significantly reduced any omeprazole induced increases in basal and meal stimulated peak and integrated serum gastrin levels; serum pepsinogen A and C values were significantly inhibited too. Serum gastrin values during combined therapy were not significantly different from those during placebo treatment, whereas pepsinogen A and C levels were still significantly raised. On the day after stopping combined therapy, basal and meal stimulated peak and integrated serum gastrin and serum pepsinogen C (but not pepsinogen A) levels were not significantly different from values obtained on the day after stopping omeprazole alone. SMS 201-995 without omeprazole significantly inhibited basal and meal stimulated peak and integrated serum gastrin levels. Pepsinogen A was also significantly inhibited by SMS 210-995, but the reduction in pepsinogen C failed to reach statistical significance. In conclusion, SMS 201-995 prevents basal and meal stimulated increases in serum gastrin during omeprazole therapy. This finding may have clinical importance in the few patients who have pronounced hypergastrinaemia because of profound long acting acid inhibition.
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PMID:Inhibition of omeprazole induced hypergastrinaemia by SMS 201-995, a long acting somatostatin analogue in man. 840 51

Histamine-producing enterochromaffin-like (ECL) cells are numerous in the oxyntic mucosa of the rat stomach. They respond to gastrin by secretory activation, hypertrophy and hyperplasia. They contain cytoplasmic granules (median profile diameter 120 nm), secretory vesicles (180 nm) and microvesicles (70 nm). alpha-Fluoromethylhistidine (alpha-FMH) depletes histamine from the ECL cells by inhibiting the histamine-forming enzyme histidine decarboxylase. Long-term hypergastrinemia, evoked by omeprazole, increases the ECL-cell histamine concentration. The way in which chronic histamine depletion affects omeprazole-induced ECL-cell hypertrophy, and the ways in which granules and vesicles in the ECL cells respond to alpha-FMH and/or omeprazole have been studied. Rats were treated with alpha-FMH (3 mg/kg per h subcutaneously), omeprazole (400 micromol/kg per day orally), alpha-FMH+omeprazole, or vehicle for 6 weeks. ECL cell profiles in electron micrographs were analysed panimetrically. The results show that the omeprazole-evoked hypertrophy of the ECL cells is not affected by depletion of ECL-cell histamine, thereby supporting the view that ECL-cell histamine is not important for full expression of the gastrin-evoked trophic effects on the ECL cells. The loss of ECL-cell histamine following treatment with alpha-FMH and with alpha-FMH+omeprazole is associated with a greatly reduced size of the secretory vesicle compartment. The granules, on the other hand, are unaffected by alpha-FMH and alpha-FMH+omeprazole. Omeprazole treatment leads to the appearance of numerous vacuoles (with profile diameter greater than 500 nm); such vacuoles are not observed in the ECL cells of rats treated with alpha-FMH or alpha-FMH+omeprazole. The omeprazole-induced increase in ECL-cell histamine is associated with an increase in the compartment composed of secretory vesicles and vacuoles. The findings support the hypothesis that secretory vesicles (and vacuoles) represent a major storage site of ECL-cell histamine.
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PMID:Ultrastructure of enterochromaffin-like cells in rat stomach: effects of alpha-fluoromethylhistidine-evoked histamine depletion and hypergastrinemia. 859 76

Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional pirenzepine treatment is also effective in suppressing acid secretion.
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PMID:Effects of pirenzepine on omeprazole-induced hypergastrinemia and acid suppression in peptic ulcer patients. 868 May 34

1. Vesicular monoamine transporters (VMATs) translocate monoamines from the cytoplasm into secretory vesicles of endocrine cells and neurones, but they have limited affinity for histamine, and the identity of the vesicular transporter for this monoamine is uncertain. The aims of the present study were to characterize VMAT representatives in rat gastric corpus, and to determine if their expression was regulated by factors that modulate histamine biosynthesis. 2. Polymerase chain reaction (PCR) cloning using oligonucleotide primers to DNA sequences conserved within the VMAT family provided evidence for VMAT2, but not VMAT1 in rat gastric corpus. Northern analysis using a VMAT2 complementary RNA probe revealed a single 4 kb mRNA species in corpus endocrine cells. 3. In rats treated for up to 5 days with the H(+)-K(+)-ATPase inhibitor omeprazole, VMAT2, histidine decarboxylase and chromogranin A mRNA abundance in gastric corpus, and plasma gastrin concentrations increased progressively. Omeprazole also elevated VMAT2 expression in rats fasted for 48 h, but fasting alone, or refeeding fasted animals had no effect. 4. The results are consistent with a role for VMAT2 in the transport of histamine into enterochromaffin-like cell secretory vesicles, and with upregulation of the transporter to accommodate the increased histamine biosynthesis and secretion that accompanies achlorhydria.
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PMID:Expression and regulation of a vesicular monoamine transporter in rat stomach: a putative histamine transporter. 874 92

We defined optimal Helicobacter pylori (Hp) treatment as Hp eradication rate about 90%, well-tolerated with few side-effects. Two centers carried out randomized trials including 90 patients (74% men, 26% women, ages ranging from 18 to 65, mean age 42 +/- 8) with active duodenal ulcers (DU). Patients were treated with the combination of Omeprazole (O) 20 mg bd + Clarithromycin (C) 250 mg bd + Tinidazole (T) (500 mg bd) or with Lansoprazole (L) 15 mg bd + Amoxicillin (A) 750 mg bd + Metronidazole (M) 500 mg bd administered for one week. The DU healing rate was evaluated by endoscopy and the Hp status by rapid urease CLO-test and 14C-urea breath test (UBT). The healing rate of the DU in a group treated with the combination of O + C + T was 91% and in group treated with L + A + M was 93%. The eradication of Hp in group O + C + T and L + A + M averaged 91% and 87%, respectively. There was no statistically significant difference in the DU healing rate and the Hp eradication rate between these two groups. Both treatments were accompanied by a marked rise in the basal and postprandial plasma gastrin levels and the rise in the intragastric pH but these alterations returned to the pre-treatment values 4 weeks after the termination of the therapy. Both treatments were well tolerated and the only side effect was the taste disturbance observed in few patents treated with O + C + T. None of patients discontinued the treatment because of the adverse events. We conclude that one week treatment using O + C + T or L + A + M are highly and equally effective in the healing of DU and in the eradication of Hp.
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PMID:One week treatment with omeprazole, clarithromycin and tinidazole or lansoprazole, amoxicillin and metronidazole for cure of Helicobacter pylori infection in duodenal ulcer patients. 877 3

We investigated whether duodenogastric reflux (DGR) together with gastroesophageal reflux causes growth stimulation of the foregut mucosa and if additional gastric acid suppression enhances the effect of DGR. DGR was induced in rats using a split gastroenterostomy. A cardiomyotomy was performed across the gastroeophageal junction in order to enhance reflux into the esophagus. DGR rats were divided into six subgroups: DGR, DGR + truncal vagotomy, DGR + omeprazole, DGR + gastrin receptor blockade, DGR + omeprazole + gastrin receptor blockade, and DGR + gastrin. Two sham groups, one with and one without omeprazole treatment, served as controls. DGR significantly increased the weight and DNA content of the esophageal and gastric mucosa, which was further enhanced by vagotomy or omeprazole. Histology revealed foveolar hyperplasia in the stomach and esophageal mucosal hyperplasia in these groups. In addition, severe esophagitis was found in the DGR group receiving omeprazole. Omeprazole without DGR had no growth-stimulating effect on the foregut mucosa. DGR-induced growth stimulation was accompanied by hypergastrinemia. Increased growth in the stomach but not the esophagus was inhibited by gastrin receptor blockade. Gastrin administration did not result in enhancement of DGR-induced growth stimulation of the foregut mucosa. It is concluded that DGR, often present in severe reflux esophagitis, causes mucosal growth of the foregut of rats. This trophic response may explain why severe reflux esophagitis is associated with an increased risk of esophageal adenocarcinoma. DGR-induced growth stimulation of the foregut is potentiated by gastric acid suppression, suggesting that chronic antisecretory medication in gastroesophageal reflux may not always be advisable. Omeprazole + DGR caused severe esophageal damage, which may explain why antisecretory medication may fail to heal severe reflux esophagitis.
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PMID:Duodenogastric reflux causes growth stimulation of foregut mucosa potentiated by gastric acid blockade. 894 68


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