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)

This multicenter, randomized, double-blind, 8-wk study compared the new H+/K(+)-ATPase inhibitor, lansoprazole, 30 mg daily, to ranitidine 150 mg bid for treatment of erosive reflux esophagitis resistant to histamine-2 receptor antagonists (H2RA). Patients were evaluated after 2, 4, 6, and 8 wk of treatment by symptom assessment and endoscopy. Healing rates for lansoprazole were 71%, 80%, 88%, and 89% at 2, 4, 6, and 8 wk, respectively, compared to 21%, 33%, 45%, and 38% for ranitidine (p < 0.001 at all points). Lansoprazole was significantly more effective than ranitidine for relief of heartburn and reduction of antacid tablet use. Increases in serum gastrin concentrations between the baseline and the 8-wk visit were greater in lansoprazole-treated than in ranitidine-treated patients. Lansoprazole was safe and well tolerated. In patients with erosive reflux esophagitis resistant to standard doses of H2RA, lansoprazole 30 mg/day is more effective than continuation of an H2RA (ranitidine 150 mg bid) for healing of esophagitis and improvement of symptoms.
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PMID:Treatment of reflux esophagitis resistant to H2-receptor antagonists with lansoprazole, a new H+/K(+)-ATPase inhibitor: a controlled, double-blind study. Lansoprazole Study Group. 810 95

H+, K(+)-ATPase inhibitors such as omeprazole are the antisecretory agents of choice for the management of gastric acid hypersecretory states, including the Zollinger-Ellison syndrome. However, long-term follow-up data on the overall efficacy and safety of these agents in large numbers of patients are lacking. In the current study we examined the long-term efficacy and safety of omeprazole in 116 patients with Zollinger-Ellison syndrome treated with oral omeprazole at a single centre for up to 114 months (mean +/- S.E.M. = 38 +/- 3 months). The initial omeprazole maintenance dose was established according to the acute upward dose titration method in 89/116 patients (77%). Gastric acid output was effectively controlled using 60 mg of omeprazole once daily in 41/89 patients (46%) and 22/89 patients (25%) required twice daily omeprazole therapy. The mean ranitidine equivalent dose for patients who required 60 mg omeprazole once daily (2.5 +/- 0.2 g/day) was significantly lower than the mean ranitidine equivalent dose for patients who required more than 60 mg omeprazole once daily (4.3 +/- 0.3 g/day). Long-term omeprazole maintenance therapy was discontinued in 36/116 patients (31%) but in no cases was discontinuation due either to drug-induced side-effects or uncontrolled gastric acid output. Fasting serum gastrin levels were significantly elevated above pre-treatment levels at only one time point during follow-up and were likely due to tumour growth rather than a drug effect. The final long-term omeprazole maintenance doses were lower than the initial doses but correlated closely with the pre-omeprazole basal acid output (r = 0.41, P < 0.001) and ranitidine equivalent dose requirements (r = 0.49, P < 0.001). We conclude that omeprazole effectively and safely controls gastric acid hypersecretion in all patients with Zollinger-Ellison syndrome for up to nine years without evidence by tachyphylaxis.
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PMID:Use of omeprazole in Zollinger-Ellison syndrome: a prospective nine-year study of efficacy and safety. 816 65

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

A 63-year-old woman was diagnosed as autoimmune gastritis by the presence of serum antibody against alpha-subunit of gastric H+,K(+)-ATPase. The patient did not have pernicious anemia, but showed achlorhydria, marked hypergastrinemia, enterochromaffin-like cell hyperplasia and an extremely high histidine decarboxylase activity in the gastric fundic mucosa. Intragastric acidification by infusion of hydrochloric acid via a nasogastric tube induced a transient reduction of serum gastrin level and fundic mucosal histidine decarboxylase activity. A marked increase in fundic mucosal histidine decarboxylase activity as well as hypergastrinemia appears to be the pathophysiologic response to achlorhydria caused by autoimmunity against gastric H+,K(+)-ATPase.
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PMID:Marked increase in fundic mucosal histidine decarboxylase activity in a patient with H+,K(+)-ATPase antibody-positive autoimmune gastritis. 828 44

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

The parietal cells, which are responsible for the production of gastric HCl acid, are uniquely equipped for high-gradient ion transport. Adequate energy is supplied by oxidative metabolism in the mitochondria, which occupy an exceptionally high proportion of the cytoplasmic volume. Another characteristic feature is the secretory canaliculi. These are tortuous small channels lined by microvilli which penetrate all parts of the cytoplasm and which expand during stimulation of secretion. The activity of the parietal cell is controlled by receptors for acetylcholine, histamine and gastrin on the basolateral cell membrane. Stimulation of these receptors modulates the levels of protein kinases in the cell and brings about the changes from resting to stimulated structure. A key role in the production of acid is played by the gastric acid pump, also known as the H+, K(+)-ATPase, which exports hydrogen ions in 1:1 exchange for potassium ions. This protein is a member of the P-type ATP-driven ion pumps and appears to be uniquely located in the parietal cell. The gastric acid pump is found in the tubulovesicular membranes of the resting cell and moves to the membrane lining the secretory canaliculus when acid secretion is stimulated. Functional acid secretion also requires the presence of KCl pathways in the secretory membrane in order to supply the acid pump with a source of potassium ions. For each hydrogen ion secreted across the secretory membrane, one bicarbonate ion is generated in the cytoplasm and is transported across the basolateral membrane in exchange for chloride. The movement of ions across the apical membrane is followed osmotically by water, resulting in the secretion of 160 mM HCl from the parietal cell.
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PMID:Cell biology of gastric acid secretion. 838 69

The activity of gastric parietal cells in terms of hydrochloric acid (HCl) secretion is regulated by the interaction of stimulatory substances (e.g. gastrin) and inhibitors (e.g. somatostatin) acting in an endocrine and paracrine mode, as well as luminal factors. In the present study the following parameters were measured: the synthesis (mRNA), storage (tissue peptide concentration) and secretion (plasma peptide concentration) of somatostatin and gastrin following short-term treatment of rats with pentagastrin (acid stimulant), secretin, omeprazole (reduces gastric acidity by inactivating gastric H/K ATPase) and the somatostatin analogue octreotide (reduces gastric acidity by inhibiting both the parietal cell and gastrin). The mRNA coding for H/K ATPase and carbonic anhydrase II (CA II), the two enzymes responsible for the generation of hydrogen ions from the parietal cell, were also quantitated. In response to octreotide, somatostatin peptide and mRNA levels in the fundus rose to 180 +/- 16% (P < 0.001) and 1073 +/- 356% (P < 0.05) of control, respectively. In contrast, octreotide caused a decrease in antral somatostatin peptide and its mRNA did not change significantly. No significant changes in synthesis, secretion or storage of gastrin were observed except for omeprazole induced hypergastrinaemia (580 +/- 76%, P < 0.001). H/K ATPase and CA II mRNA were largely unaffected except for an increase in CA II mRNA following octreotide and a decrease in H/K ATPase mRNA after pentagastrin. These data support the concept of the differential control of antral and fundic somatostatin synthesis and provide evidence for a regulatory loop by which somatostatin can influence its own synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secretory and biosynthetic responses of gastrin and somatostatin to acute changes in gastric acidity. 852 6

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

The presence of subunit proteins, 1H9 for the alpha-subunit and 2B6 for the beta-subunit, of H(+)-K+ ATPase and its activity in tubulovesicles and intracellular canaliculi of gastric parietal cells were immunocytochemically and enzyme cytochemically examined. Specimens were taken from healthy human volunteers by endoscopic biopsy in resting, tetragastrin-stimulated and omeprazole-inhibited conditions. H(+)-K+ ATPase was present in both intracellular canaliculi and tubulovesicles in these three conditions. Gold particles of the alpha-subunit decreased in number, and those showing the beta-subunit increased under both gastrin-stimulating and omeprazole-inhibiting conditions compared with parietal cells in the resting state. We suggest that the administration of tetragastrin and omeprazole alter the turnover rate of each subunit of H(+)-K+ ATPase, resulting in the difference of the proportions of alpha- and beta-subunits. Moreover, the activity of H(+)-K+ ATPase was detected strongly beneath the membrane of microvilli and weakly in that of tubulovesicles under these three conditions. After 7 days of daily oral omeprazole intake, H(+)-K+ ATPase in parietal cells were detected in intracellular canaliculi and tubulovesicles. However, the H(+)-K+ ATPase activity in tubulovesicles was diminished 1 h after omeprazole intake, and the activity in intracellular canaliculi was completely inhibited even 3 h after omeprazole administration. These results show that omeprazole inhibited the H(+)-K+ ATPase activity in both intracellular canaliculi and tubulovesicles.
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PMID:An immuno- and enzyme cytochemical study of the H(+)-K+ ATPase in human parietal cells after administration of tetragastrin and omeprazole. 923 84


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