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)

APUDomas are rare tumours originating from a variety of endocrine cells localized in different organs. Acute complications from APUDomas usually result from the increased biosynthesis and release of bioactive amines or polypeptide hormones by the tumour. Less frequently, bleeding or compression by the tumour can occur requiring emergency surgery. Increased gastrin production by gastrinomas is the cause of ZES (peptic ulceration and diarrhoea) by gastrin effects on gastric acid secretion. Volume depletion, hypokalaemia, severe bleeding, duodenal perforation, oesophageal stricture and pyloric stenosis are the most dramatic complications. Treatment of these complications and their prevention has been facilitated by the availability of antagonists to H2 receptors and H(+)-K+ proton pump. These medications should control acid output in every patient with ZES. Frequent manifestations of carcinoid tumours, VIPomas and medullary thyroid carcinomas are flushing and diarrhoea. Octreotide, a long-acting somatostatin analogue, has markedly changed the management of these patients, their symptoms decreasing in severity or disappearing in most cases. Octreotide has also been used with success in the prevention and treatment of the carcinoid crisis, a dreaded complication of carcinoid tumours. A better understanding of the pathophysiology of APUDomas has enabled new treatment designs which have considerably ameliorated the quality of life of patients affected by these tumours; efforts must be continued to affect their life expectancy.
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PMID:APUDomas: acute complications and their medical management. 131 Aug 47

In recent studies, proton pump inhibitors, such as omeprazole, were found to be transformed into sulfenamide derivatives in the acid space of isolated parietal cells. It is considered that these sulfenamide derivatives mainly inhibit H+, K(+)-ATPase activity. To clarify the inhibitory mechanism of proton pump inhibitors, we studied the effect on acid secretion of the isolated parietal cells. Proton pump inhibitors inhibited histamine-, carbachol- and gastrin-stimulated 14C-aminopyrine accumulation. Db-cAMP stimulation was also inhibited by these inhibitors. Consequently, it is believed that the origin of H+, K(+)-ATPase was located in the final stage of the acid production.
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PMID:[Studies on the intracellular pharmacodynamic properties of proton pump inhibitors and the inhibitory mechanism of acid secretion]. 131 83

E-3810 and AG-1749, new proton pump inhibitors, were administrated in single doses or over a long period of time in order to evaluate their effect on the rat stomach. E-3810 inhibited gastric acid secretion for a shorter period of time than AG-1749 in both the single dose and long-term administration. While hypergastrinemia persisted with long-term administration of AG-1749, serum gastrin levels returned to normal upon cessation of treatment with E-3810. Both E-3810 and AG-1749 caused vacuolar formation of parietal cells and an increase in gastric acid secretion after cessation of long-term treatment, suggesting that these changes are common after treatment with proton pump inhibitors.
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PMID:[Changes in the rat stomach after long-term administration of proton pump inhibitors (AG-1749 and E-3810)]. 131 85

Proton pump inhibitor is a compound recently applied for the treatment of peptic ulcers for its strong action to inhibit the gastric acid secretion. It works through inhibition of H+, K(+)-ATPase, so called proton pump, on the luminal surface of secretory canaliculi in the parietal cells, showing remarkable characteristics in the inhibition of gastric acid secretion; e.g., the long-acting and complete inhibition. At neutral pH, the unionized form of this compound as a weak base is lipophilic, and passes through the cell membrane to accumulate as the ionized form in an acidic environment in the secretory canaliculi of parietal cells, where it is transformed to an active molecule which binds covalently to the active site of H+, K(+)-ATPase, forming a highly stable complex. The long-acting and complete inhibition of gastric acid secretion by this compound is derived from this physico-chemical nature. The above characteristics of the proton pump inhibitor have been confirmed with the basal, stimulated and nocturnal gastric acid secretion and the 24-hour intragastric pH of healthy volunteers by several investigators prior to its nation-wide clinical trial in Japan. On the other hand, the increased endocrine and exocrine secretion, such as pepsin secretion and gastrin release, and the increased turnover of gastrointestinal endocrine cells by this compound have been reported in animal models, probably due to its accumulation in the acidic environment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Characteristic features of proton pump inhibitors in the inhibition of gastric acid secretion: long-acting and complete inhibition]. 131 89

Gastric acid secretion is regulated by an intricate interplay of neural (acetylcholine), hormonal (gastrin), and paracrine (histamine, somatostatin) mechanisms. Receptors for each of these agents and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of acetylcholine and gastrin is mediated by an increase in cytosolic calcium, whereas that of histamine is mediated by activation of adenylate cyclase and generation of cAMP. Strong potentiation between histamine and either gastrin or acetylcholine reflects postreceptor interaction between the distinct pathways as well as the ability of acetylcholine and gastrin to release histamine from mucosal ECL cells. The inhibitory effects of somatostatin on acid secretion are mediated by receptors coupled by 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 has led to the development of potent drugs capable of inhibiting acid secretion. These include competitive antagonists that interact with stimulatory receptors (e.g., histamine H2-receptor antagonists) as well as noncompetitive inhibitors of H+K(+)-ATPase (e.g., omeprazole). The histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, and nizatidine) 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 interference with the absorption, metabolism, and elimination of various drugs. Omeprazole is a weak base that reaches the parietal cell through the bloodstream, diffuses through the cytoplasm, and becomes activated and trapped as a sulfenamide in the acidic canaliculus of the parietal cell. It covalently binds to H+K(+)-ATPase, thereby irreversibly blocking acid secretion in response to all modes of stimulation. The main drawback to its use is its extreme potency, which leads to virtual anacidity, gastrin and ECL cell hyperplasia, hypergastrinemia, and, in rats, to the development of carcinoid tumors.
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PMID:Control of gastric acid secretion. Histamine H2-receptor antagonists and H+K(+)-ATPase inhibitors. 135 65

Recently, antisecretory drugs such as H2-receptor antagonists (H2-RA) or proton pump inhibitor have been used for peptic ulcer patients widely in Japan. However, there are possibilities that long term administration of H2-RA might cause changes in intragastric environment. The present study was designed to clarify the changes of surgical treatment in Japan Surgical Society training hospitals, before and after introduction of H2-RA. Serum gastrin and antral G-cell number was measured after administration of H2-RA (1 mg/kg 14 days continuous infusion) in rat. Also, acid secretion and gastrin response stimulated by adrenalin (40 ng/kg.min) were measured in duodenal ulcer patients. 1) In the view of surgical treatment, elective operation highly decreased after the introduction of H2-receptor antagonists, and showed the increase of the rate of emergency operation up to 70%. 2) Hypergastrinemia and antral G cell hyperplasia were observed after administration of H2-RA in rats. 3) Acid secretion stimulated by adrenalin which is considered as antral G cell dependent, showed a higher response in H2-RA treated cases than in those untreated. 4) Antrectomy was carried out in 43.4% of the patients treated with H2-RA versus 18.9% to the patients untreated.
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PMID:[Problems in ulcer surgery after the introduction of H2-receptor antagonists]. 136 54

To investigate the effect of 6 weeks administration of proton pump inhibitor (omeprazole) and H2-receptor antagonist (cimetidine) on gastric histamine synthesis and acid secretion, we studied experimentally in the rat stomach. Then gastric mucosal histamine concentration, histidine decarboxylase (HDC) activity and serum gastrin concentration, and HDC positive cell number were examined in time-course. The 6 weeks administration of omeprazole caused more increase of HDC positive cells than cimetidine. After cessation of administration with omeprazole, high plasma gastrin level immediately reduced. However the increase of gastric mucosal HDC activity and histamine concentration were prolonged, compared with cimetidine. These findings suggest to affect differently between omeprazole and cimetidine on gastric acid secretion after cessation of long-term treatment.
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PMID:[Effect of long-term administration of antisecretary drugs on rat gastric histamine synthesis and acid secretion--compare with omeprazole and cimetidine]. 140 68

Hyperplasia of the oxyntic enterochromaffinlike cells in response to long-lasting blockade of acid secretion is closely related to hypergastrinemia. In the present study, the effect of a specific gastrin receptor antagonist on proton pump inhibitor-induced changes on serum gastrin levels, mucosal height, as well as gastrin- and enterochromaffin-like cells was investigated in rats. The proton pump inhibitor BY 308 or the vehicle methylcellulose [Methocel (controls)] was administered for 2 weeks in the presence and absence of the gastrin receptor antagonist PD 136450 (CAM 1189). BY 308 significantly increased serum gastrin levels, gastrin cell density, and antral gastrin concentration. Concomitant application of PD 136450 did not alter this response. In the oxyntic stomach, mucosal height, enterochromaffinlike cell density, labeling index of enterochromaffinlike cells, and histamine concentration were elevated after treatment with BY 308. These increases were almost completely abolished by PD 136450. Even in normogastrinemic control rats, PD 136450 significantly decreased mucosal height of the oxyntic part of the stomach and the labeling index of enterochromaffinlike cells. The results show that (a) trophic effects of drug-induced achlorhydria are mediated by gastrin; (b) even in control rats (normogastrinemic), gastrin is a trophic factor for the oxyntic mucosa; and (c) antral gastrin cell hyperplasia in states of chronic achlorhydria is not mediated by gastrin itself.
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PMID:Effect of gastrin receptor blockade on endocrine cells in rats during achlorhydria. 142 80

Omeprazole, a proton pump inhibitor was used for premedication for general anesthesia, and its effects on gastric secretion and serum gastrin level were investigated in 60 patients. The patients were divided into the following 4 groups and each group received one of the following medications; (I) a tablet of omeprazole 20 mg before sleep at the night before the surgery, (II) a tablet 2 hours before the induction of anesthesia, (III) one on the night before and another tablet 2 hours before the induction, or (0) no tablet. In the patients who received any dose of the drug, the volume of gastric juice at the beginning of the surgery was significantly less than that in those who received no drug (P less than 0.05). Gastric pH showed a tendency to increase depending on the dose of omeprazole (0 less than I less than II less than III), but it was not significant. No significant change in serum gastrin level was observed in this study. A 20 mg omeprazole tablet may not be adequate as the premedication for general anesthesia.
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PMID:[Use of omeprazole for premedication]. 143 54

Omeprazole, an inhibitor of gastric acid secretion, was administered to rats at a dosage of 20 mg/kg/day for 14 and 35 days, and subsequent changes in subcellular structures of parietal cells were analyzed using morphometry and immunocytochemistry. Plasma gastrin levels were also examined, showing two times higher levels in the experimental groups than in the non-treated control. The volume and surface densities significantly decreased in tubulovesicles of the cells in the experimental rats. In the long term treatment of omeprazole (35 days), the volume density of microvilli on the membranes of secretory canaliculi in the cells also decreased significantly, whereas that of lysosomes clearly increased. By electron microscopy, many dense bodies of various shapes often appeared in the cytoplasm of parietal cells after the omeprazole treatment. Immunocytochemistry revealed that large granular immunodeposits for cathepsin B increase in the epithelial cells of the gastric glands after omeprazole treatment. These results suggest that omeprazole induces quantitatively significant decreases in both tubulovesicles and canalicular microvilli. The decreases in these membrane structures may possibly be ascribed to the degradation of the membrane in lysosomes; the proton pump on the membranes bound irreversibly with omeprazole is believed destined to be degraded in lysosomes.
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PMID:Changes in subcellular structures of parietal cells in the rat gastric gland after omeprazole. 149 49


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