Disease relevance of GAST

• While it has been hypothesized that gastrin, a stimulator of gastric acid secretion, is also a neurotransmitter and a stimulator of cell proliferation in various normal and neoplastic tissues, its effect on astrocytic brain tumors has not been actively investigated [1].
• Human gastrin: a Helicobacter pylori--specific growth factor [2].
• Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin [3].
• Gastrin induces proliferation in Barrett's metaplasia through activation of the CCK2 receptor [4].
• This may have implications for the management of patients with Barrett's esophagus in whom gastrin is elevated by acid-suppression therapy [4].

Psychiatry related information on GAST

• Decreased gastrin concentrations may play a role in the gastric symptoms associated with anorexia nervosa [5].
• The brain cholecystokinin-B/gastrin receptor (CCK-B/gastrin) has been implicated in mediating anxiety, panic attacks, satiety, and the perception of pain [6].
• The nature and developmental profile of pancreatic gastrin and somatostatin were determined in the ovine fetus, a model considered relevant to human development [7].
• Interactions of cholecystokinin (CCK-PZ) and gastrin on motor activity of isolated guinea-pig antrum and fundus [8].
• Under the conditions of this study, which reproduce those of excessive alcohol drinking, alcohol and alcoholic beverages did not stimulate pancreatic enzyme secretion, although wine and beer increased the release of gastrin and cholecystokinin [9].

High impact information on GAST

• Cholecystokinin and gastrin receptors [10].
• Recent studies have demonstrated that it is feasible to regenerate and expand the beta-cell mass by the application of hormones and growth factors like glucagon-like peptide-1, gastrin, epidermal growth factor, and others [11].
• The conversion of inactive peptide precursors to their active forms takes place during transit along the secretory pathway and is only completed after sequestration in secretory granules. the processing of the gastrin precursor provides a useful model for studying prohormone processing [12].
• Brief report: a duodenal gastrinoma in a patient with diarrhea and normal serum gastrin concentrations [13].
• Immunocytochemical analysis revealed the presence of gastrin in all the duodenal tumors and in their lymph-node metastases [14].

Chemical compound and disease context of GAST

• Influence of COX-2 inhibition by rofecoxib on serum and tumor progastrin and gastrin levels and expression of PPARgamma and apoptosis-related proteins in gastric cancer patients [15].
• Gastrin and pentagastrin enhance the tumour proliferation of human stable cultured gastric adenocarcinoma cells [16].
• Other gastrin agonists include beta-adrenergic agents, acetylcholine, gastrin-releasing peptide (bombesin), TGF-alpha, and possibly the gastric pathogen, Helicobacter pylori [17].
• Serum gastrin and gastric endocrine cell numerical densities were examined in 22 patients with long-standing Zollinger-Ellison syndrome who were receiving either ranitidine, omeprazole, or other antisecretory drugs (SMS 201-995 or pirenzepine with or without ranitidine) for long periods of time [18].
• Furthermore, pertussis toxin pretreatment reversed the ability of somatostatin to inhibit secretin-induced increase in gastrin release and activation of adenylate cyclase [19].

Biological context of GAST

• Influence of gastrin on human astrocytic tumor cell proliferation [1].
• Furthermore, the adenylate cyclase and phosphatidyl inositide second messenger systems seem to be intracellular mediators of gastrin secretion from human antral G cells [20].
• It is unknown whether gastrin can influence cellular events in the esophagus in Barrett's. METHODS: Reverse-transcription polymerase chain reaction (RT-PCR) and northern analysis for the cholecystokinin (CCK(2)) receptor were performed on normal, inflamed, metaplastic, and malignant esophageal mucosa [4].
• Gastrin also acts as a potent cell-growth factor that has been implicated in a variety of normal and abnormal biological processes including maintenance of the gastric mucosa, proliferation of enterochromaffin-like cells, and neoplastic transformation [21].
• The binding of gastrin or CCK to their common cognate receptor triggers the activation of multiple signal transduction pathways that relay the mitogenic signal to the nucleus and promote cell proliferation [21].

Anatomical context of GAST

• RESULTS: At specific concentrations, added gastrin increased the cellular proliferation of three established astrocytic cell lines (A172, Hs683, and SW1088), decreased it in two (U373 and T98G), and was without effect on the remaining five [1].
• CONCLUSIONS: Gastrin induces proliferation via the CCK(2) receptor in Barrett's mucosa [4].
• Gastrin secretion from human antral G cells in culture [20].
• In contrast to the pancreas, binding of 125I-BH-CCK-8 to the gallbladder muscle was inhibited with high affinity by CCK-8 and lorglumide but was replaced to a small degree by gastrin and L365,260 [22].
• Gastrin cells were few and occurred in the proximal duodenum only [23].

Associations of GAST with chemical compounds

• The effects of added gastrin (at 0.01, 0.1, and microM) and the gastrin/CCK antagonists L-365,260, CI-988, L-364,718, and JMV 234 (each at 0.01, 0.1, and 1 microM) on the cellular proliferation rates of the 10 cell lines were indirectly measured by use of the colorimetric tetrazolium assay [1].
• The influence of gastrin (at 0.01 microM) on the cellular proliferation of primary cultures from nine freshly explanted astrocytic tumors was assessed by means of tritiated thymidine uptake and autoradiography [1].
• Controls consisting of cholecystokinin and pentagastrin inhibited gastrin uptake but did not stimulate growth [2].
• METHODS: Acini isolated from human pancreas were treated with CCK receptor agonists, CCK-8 and gastrin, and an agonist for m3 muscarinic acetylcholine receptors (m3 AchR), carbachol [24].
• Forskolin, A23187, and beta-phorbol 12 myristate 13-acetate stimulated basal gastrin secretion from cultured human G cells in a concentration-dependent fashion [20].

Physical interactions of GAST

• The purpose of this study was to explore the intracellular events of colorectal cancer cells after gastrin binding to CCK2R [25].
• Serotonin and gastrin/cholecystokinin-like immunoreactive neurons in the larval retrocerebral complex of the blowfly Calliphora erythrocephala [26].
• In addition, somatostatin binding to cytosol from gastric (fundus and antrum) mucosa and fasting serum gastrin levels and serum gastrin response to a standard breakfast were also studied [27].
• However, the specific gastrin binding was not inhibited by glucagon, insulin, acetylcholine, atropine, histamine, or cimetidine [28].
• Electrophoretic mobility shift assays confirmed that KLF4 is able to bind all three gastrin responsive elements [29].

Enzymatic interactions of GAST

• Exocytosis of histamine following gastrin stimulation and Ca(2+) entry across the plasma membrane is catalyzed by synaptobrevin and synaptosomal-associated protein of 25 kDa, both characterized as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein [30].
• We report here that synthetic human gastrin 17 is phosphorylated by the EGF-stimulated tyrosine kinase of A431 cell membranes [31].

Regulatory relationships of GAST

• CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67% [32].
• Somatostatin potently suppressed forskolin- and bombesin-mediated gastrin release but did not significantly alter basal gastrin levels [20].
• Gastrin-induced cyclooxygenase-2 expression in Barrett's carcinogenesis [33].
• Gastrin induced membrane translocation of PKC-alpha [34].
• Our results suggest that activation of CCK2R by gastrin stimulates heterotrimeric G-protein Gq and G(12/13) mediated intracellular signal transduction pathway in colon cancer cells [25].

Other interactions of GAST

• Postprandial Gs levels were also elevated, whereas VIP levels were markedly reduced in patients versus controls; these differences were most marked in stage II patients [35].
• Hormone levels of patients and controls did not differ between the test meal situations, which indicated that some other component of the test meals might have been responsible for altered Prl and Gs levels [35].
• After a 2-day incubation period, gastrin- and somatostatin-containing cells accounted for 15% and 5%, respectively, of the total adhered-cell population [20].
• RESULTS: High concentrations of CCK-B-gastrin receptors were detected in the midglandular region of the human fundic mucosa [36].
• CONCLUSIONS: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion [32].

Analytical, diagnostic and therapeutic context of GAST

• Gastrin decreased cellular proliferation in one primary astrocytic tumor cell culture, stimulated it in five, and had no apparent effect in the remaining three [1].
• Specifically, human and animal models of hypergastrinemia and hypogastrinemia have been described in vivo, and several cells that express cholecystokinin (CCK)B/gastrin receptors have been used for analysis of intracellular signaling pathways initiated by biologically active amidated gastrins [21].
• This G/CCK-LI diluted in parallel to mammalian gastrin in radioimmunoassays using two antisera differing in their specificities for the bioactive COOH-terminal region of mammalian G/CCK [37].
• Gastrin/cholecystokinin-like immunoreactivity (G/CCK-LI) was localized by immunocytochemistry in neurons in the central nervous system of Aplysia californica [37].
• Gastrin mRNA measured by in situ hybridization was present in most CCK-B receptor-positive small cell lung cancers, breast tumors, and ovarian tumors, representing the molecular basis of a possible autocrine growth regulation of these tumors [38].

References