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)

Helicobacter pylori infection causes inflammation of the gastric and duodenal mucosa, which results in a disturbance of the regulation of gastrin, gastric acid, and pepsin secretion. Acid secretion may be diminished, normal, or increased, depending on the stage of H. pylori infection, although the meal-stimulated gastrin response is invariably elevated. The exact mechanisms involved are not known, but probably involve the release of cytokines in response to bacterial products initiating mucosal inflammation. Helicobacter pylori is suppressed, although not eradicated, by proton pump inhibitors. In various dose combinations with amoxycillin, omeprazole in a twice daily dose of up to 40 mg b.i.d. eradicates the organism in up to 82% of patients. This synergistic effect may be due to the direct effects of omeprazole, the protection of amoxycillin from acid degradation, or the enhancement of host defense mechanisms accompanying acid suppression.
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PMID:Hp and pH--the relevance of gastric acid to the treatment of Helicobacter pylori infection. 792 Nov 45

The present strategies for the management of peptic ulceration are well tolerated and clinically effective. Histamine H2-receptor antagonists can be used for mild to moderate disease, and proton pump inhibitors are of particular benefit for patients with severe peptic ulceration and the Zollinger-Ellison syndrome. However, none of these treatments provides protection against recurrent ulceration, except when taken as long-term continuous treatment. Long-term exposure to pharmacological agents raises problems of safety, particularly relating to a lack of intragastric acidity. In addition, the accelerated development of atrophic gastritis in patients receiving omeprazole requires investigation and assessment. It is unlikely that there will be any major development in the area of control of gastric acid secretion, except perhaps the introduction of specific immunization against gastrin. However, the clinical benefit of this strategy awaits assessment. The main area for development must be the introduction of convenient and effective regimens for the eradication of Helicobacter pylori infection. Existing regimens are either simpler and relatively ineffective, or too complicated for widespread application. Bearing in mind the long gestation period of any new drug, it seems likely that the only innovative drug that will be introduced for the management of peptic ulceration before the millennium will be ranitidine bismuth citrate, an antisecretory anti-H. pylori drug that will usually be used in combination with an antibiotic.
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PMID:Treatment of peptic ulcers from now to the millennium. 794 62

Gastric acid secretion is precisely regulated by neural (acetylcholine), hormonal (gastrin), and paracrine (histamine; somatostatin) mechanisms. The stimulatory effect of acetylcholine and gastrin is mediated via increase in cytosolic calcium, whereas that of histamine is mediated via activation of adenylate cyclase and generation of cAMP. Potentiation between histamine and either gastrin or acetylcholine may reflect postreceptor interaction between the distinct pathways and/or the ability of gastrin and acetylcholine to release histamine from mucosal ECL cells. The prime inhibitor of acid secretion is somatostatin. Its inhibitory paracrine effect is mediated predominantly by receptors coupled via guanine nucleotide binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+,K(+)-ATPase, the proton pump of the parietal cell. Precise information on the mechanisms involved in gastric acid secretion and the identification of specific receptor subtypes has led to the development of potent drugs capable of inhibiting acid secretion. These include competitive antagonists that interact with stimulatory receptors (e.g. muscarinic M1-receptor antagonists and histamine H2-receptor antagonists) as well as non-competitive inhibitors of H+,K(+)-ATPase (e.g. omeprazole). The histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine and roxatidine acetate) continue as first-line therapy for peptic ulcer disease and are effective in preventing relapse. Although they are generally well tolerated, histamine H2-receptor antagonists may cause untoward CNS, cardiac and endocrine effects, as well as interfering with the absorption, metabolism and elimination of various drugs. The dominance of the histamine H2-receptor antagonists is now being challenged by omeprazole. Omeprazole reaches the parietal cell via the bloodstream, diffuses through the cytoplasm and becomes activated and trapped as a sulfenamide in the acidic canaliculus of the parietal cell. Here, it covalently binds to H+,K(+)-ATPase, the hydrogen pump of the parietal cell, thereby irreversibly blocking acid secretion in response to all modes of stimulation. The main potential drawback to its use is its extreme potency which sometimes leads to virtual anacidity, gastrin cell hyperplasia, hypergastrinaemia and, in rats, to the development of carcinoid tumours. The cholinergic receptor on the parietal cell has recently been identified as an M3 subtype and that on postganglionic intramural neurones of the submucosal plexus as an M1 subtype.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacology of gastric acid inhibition. 809 11

Pantoprazole, a novel proton pump inhibitor, is a potent inhibitor of gastric acid secretion. In this review, data are presented from nine controlled, prospective, clinical pharmacodynamic investigations. The effects of oral and intravenous doses of pantoprazole (administered for 5-7 days) on continuously monitored 24-h intragastric pH and serum gastrin are discussed: oral pantoprazole 20 to 80 mg/day (given in the morning before breakfast) induced a dose-related increase in both the 24-h intragastric pH and the serum gastrin profile. The effects of pantoprazole doses of 60 and 80 mg were not significantly different from those of the 40 mg dose. It was concluded that oral pantoprazole at 40 mg/day is the optimal antisecretory dose for the treatment of acid-related diseases. In two comparative studies, this dose of pantoprazole (administered before breakfast) proved to be significantly more effective than ranitidine 300 mg (given in the evening) and omeprazole 20 mg (given in the morning). Administration of oral and intravenous pantoprazole (40 mg) was found to be equipotent at increasing 24-h intragastric pH, but this finding requires further evaluation. The approximately 2-4-fold rise in median serum gastrin concentrations following several days' administration of pantoprazole 40 mg is of a comparable magnitude to that of other proton pump inhibitors. It seems unlikely that this moderate hypergastrinaemia during pantoprazole treatment should influence the human enterochromaffin-like (ECL) cell density in a clinically relevant way, but data during long-term therapy are necessary to confirm this conclusion.
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PMID:Effect of pantoprazole on 24-h intragastric pH and serum gastrin in humans. 818 Feb 93

Drug-induced achlorhydria in experimental animals results in excessive hypergastrinaemia, ECL-cell hyperplasia and ECL-cell carcinoidosis. However, these events have not been observed in long-term studies in patients receiving proton pump inhibitors. Serum gastrin levels increase only modestly during acute and long-term treatment. It is concluded that monitoring of serum gastrin levels and of fundic ECL cells is of no clinical relevance even during long-term therapy with proton pump inhibitors. The clinically available proton pump inhibitors such as pantoprazole, omeprazole and lansoprazole are well tolerated, with a low incidence of side-effects. Minor and serious side-effects classified as possibly related to proton pump therapy have been described in up to 2.5% of patients. This is the same order of magnitude as that found in patients treated with H2-receptor blockers and in placebo-treated controls. In most cases, therefore, the observed side-effects are unrelated to the intake of proton pump inhibitors. Minor adverse events include headache, diarrhoea, dizziness, pruritus and rash. Proton pump inhibitors are metabolized mainly in the liver via the cytochrome P450 system and interactions with drugs metabolized by the same system are possible. Evidence is becoming available which suggests that pantoprazole may have less potential to interact with the cytochrome P450 system than the other proton pump inhibitors. In the case of diazepam metabolism, pantoprazole had the least effect on prolongation of the diazepam effect. This may well be an advantage in the clinical use of the drug.
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PMID:Safety of proton pump inhibitors--an overview. 818 Feb 97

The gastric proton pump H+/K(+)-ATPase in the parietal cell is central to acid secretion into the stomach. We performed the following experiment to examine the pattern of expression of the alpha- and beta-subunits of the H+/K(+)-ATPase at the transcriptional level during 7 days' application of the proton pump inhibitor omeprazole, in relation to the expression of gastrin and histamine, two stimuli of gastric acid secretion. Serum gastrin concentrations and mRNA levels of antral gastrin, fundic histidine decarboxylase (HDC) and H+/K(+)-ATPase alpha- and beta-subunits were determined after 8 h, 1, 3 and 7 days. Omeprazole treatment rapidly caused an increase in the serum gastrin concentration and the antral gastrin mRNA level after 3 days. HDC mRNA expression showed a steady increase with a 5-fold induction after 1 week. However, mRNA levels of the alpha- and beta-subunits of the H+/K(+)-ATPase were unchanged during the course of omeprazole treatment. These results suggest that omeprazole inhibition of the gastric proton pump does not result in feedback activation of H+/K(+)-ATPase gene expression despite adaptive changes of the endocrine stomach.
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PMID:Expression of the gastric H+/K(+)-ATPase and histidine decarboxylase during omeprazole treatment. 818 77

Lansoprazole, a new proton pump inhibitor, selectively inhibits the H+/K(+)-ATPase. Its inhibitory effect on basal and gastrin stimulated gastric acid secretion is equal to omeprazole and stronger than that of H2-receptor antagonists. Healing rates concerning gastric and duodenal ulcers and refluxesophagitis are significantly higher compared to H2-receptor antagonists and at least comparable to omeprazole. Regarding pilot studies in H. pylori eradication therapy, lansoprazole in combination with various antibiotics is expected to show good eradication rates. Considering its excellent safety and interaction profile lansoprazole is effective and safe in treating acid related disorders.
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PMID:[Lansoprazole--profile of a new proton pump inhibitor]. 819 67

In the rat, gastrin cells are normally exposed to the stimulatory effects of food and the inhibitory influences of acid in the gastric lumen. We have studied the effects of intragastric acid on gastrin cell function in animals in which the tonic inhibitory action of acid was removed by prior treatment with the proton pump blocker omeprazole. In fasted rats with gastric fistula treated with omeprazole, instillation of acid into the stomach produced a prompt decrease in plasma gastrin, but gastrin mRNA abundance showed a modest transient increase over a period of 2 h and thereafter no change; there was also a transient increase in tissue concentrations of the gastrin precursor progastrin that was compatible with increased gastrin synthesis. Concentrations of tissue gastrins, in general, increased after acid instillation, which can be attributed to continued synthesis in the presence of suppressed gastrin release. In rats fed ad libitum, a single dose of omeprazole (which produces achlorhydria for 24-30 h) produced an increase in plasma gastrin that peaked after 24 h and declined to control levels over the following 48 h; in contrast, gastrin mRNA abundance peaked 48 h after omeprazole before declining to control levels. The results indicate that whereas gastrin release might be promptly inhibited by intragastric acid, the changes in gastrin mRNA abundance are much slower: achlorhydria increases gastrin mRNA within 24 h, but acid takes longer to depress gastrin mRNA abundance. Over periods of a few hours, gastrin release and synthesis need not, therefore, change in parallel.
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PMID:Gastrin cell responses to acidification of the achlorhydric rat stomach. 821 65

Immunoreactivities of urinary N-terminal big gastrin and serum C-terminal gastrin were determined in intact and antrectomized rats by radioimmunoassay using two antisera specific for N- and C-termini of big gastrin, respectively. Gel filtration of urine extract from intact rat showed a single giant peak of N-terminal big gastrin immunoreactivity eluted in a later position than 1-17 gastrin-34, indicating that N-terminal peptides smaller than 1-17 gastrin-34 are excreted in urine. Serum C-terminal gastrin concentration in antrectomized rats was about one sixth that in intact rats. Urinary excretion of N-terminal big gastrin in antrectomized rats was about one sixth that in intact rats. 2 week treatment with E3810, a proton pump inhibitor, (40 mg/kg/day, s.c.) induced urinary excretion of N-terminal big gastrin in parallel with a marked increase in serum C-terminal gastrin concentration in intact rats. Antrectomy completely prevented both the increase in urinary excretion of N-terminal big gastrin and the elevation of serum C-terminal gastrin induced by administration of E3810. There was an excellent correlation between serum concentration of C-terminal gastrin and urinary excretion of N-terminal big gastrin. These results suggest that urinary N-terminal big gastrin, which mostly originates from the gastric antrum, is a useful indicator of gastrin secretion in the rat.
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PMID:Effect of antrectomy and drug-induced achlorhydria on urinary excretion of N-terminal big gastrin immunoreactivity in rats. 827 33

Little data exist regarding the activity of gastric parietal and G cells in the very immature infant. Therefore, we have examined the developing human stomach for the presence and location of parietal and G cells, by using both standard histological methods and antibodies to the H+/K(+)-ATPase (proton pump), intrinsic factor and gastrin in 25 fetuses (ranging from 13-28 weeks) and in 5 infants (2-21 weeks). Parietal cell activity was noted in the body, antrum and pyloric regions in all the fetal specimens examined. However, this activity was much more limited in the infant specimens. Gastrin immunoreactivity was noted in all specimens from 18 weeks of gestation onwards; this activity was located solely in the antral and pyloric region. These results indicate that the human fetus has the potential to produce gastric acid, intrinsic factor and gastrin from the middle of the second trimester.
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PMID:When is the fetus first capable of gastric acid, intrinsic factor and gastrin secretion? 832 94


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