Disease relevance of Gast

• However, colorectal carcinoma cells may aberrantly produce gastrin and exhibit increased expression of cholecystokinin B (CCK-B)/gastrin receptors [1].
• In the human gastrinoma culture, RC-160 inhibited gastrin release significantly more than octreotide at 10(-12)- and 10(-14)-M concentrations (P < 0.01) [2].
• We previously reported that gastrin (G17) inhibits apoptosis of AR4-2J pancreatic adenocarcinoma cells, through the activation of Akt [3].
• Serum gastrin levels are responsive to many physiologic and pharmacologic factors including hyperglycemia, somatostatin, and glucagon [4].
• RESULTS: In rats with gastric ulcer, the levels of gastrin and motilin in the antral mucosa increased, but in a lesser scale in rats with ulcer kept in high temperature than in normal temperature group, while that of somatostatin was reduced [5].

Psychiatry related information on Gast

• Effect of food deprivation on rat gastric somatostatin and gastrin release [6].
• It is concluded that partial sleep deprivation compromises gastric mucosal integrity by increasing gastric acidity, plasma levels of noradrenaline, gastrin, histamine, and decreasing gastric mucosal blood flow [7].
• The levels of circulating leptin observed after 2 and 6 h of refeeding in 18-h fast rats were significantly lowered by injection of the specific gastrin/CCK-B receptor antagonist YM022 at doses that did not affect feeding behavior [8].
• A long-term change in the level of serum gastrin, caused by dietary modification, will influence the trophic effect that gastrin has on colonic mucosa as well as on colon carcinomas [9].
• BACKGROUND: Gastrin and its analogues increase the gastric acid secretion, but also enhance mucosal defense mechanisms [10].

High impact information on Gast

• By contrast, only half of gastrin molecules are tyrosine-O-sulphated and sulphation does not influence the ability of gastrin to regulate gastric acid secretion [11].
• Although phosphorylation has received most attention, tyrosine-O-sulphation is also common and has been closely investigated in the hormones gastrin and cholecystokinin (CCK) [11].
• Moreover, the disappearance of gastrin from the pancreas during the first weeks after birth parallels the appearance of CCK in the intestine [11].
• GABA affects the release of gastrin and somatostatin from rat antral mucosa [12].
• However, immune cells in the lamina propria are the only cells that showed detectable messenger RNAs for histamine, muscarinic, gastrin, and dopamine receptors by in situ hybridization histochemistry [13].

Chemical compound and disease context of Gast

• In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin release by cultured cells from a human gastrinoma [2].
• Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole-induced achlorhydria [14].
• The inhibitory action of PYY and related peptides on gastrin-stimulated histamine release and calcium signaling was eliminated by pretreatment with 200 ng/mL pertussis toxin [15].
• E. coli LPS had a weak stimulatory effect on ECL cell BrdU uptake at 10(-6) mol/L but had no effect on gastrin-stimulated BrdU uptake [16].
• The release of gastric somatostatinlike immunoreactivity and gastrin was studied in rats with chronic achlorhydria induced by the substituted benzimidazole BY 308 [17].

Biological context of Gast

• Differential gastrin gene expression in rat gastrointestinal tract and pancreas during neonatal development [18].
• The results suggest that the mechanisms determining phosphorylation and amidation of progastrin-related peptides depend on the patterns of stimulation of gastrin cells [19].
• Pancreatic gastrin is maximally expressed during late fetal gestation before the marked rise in somatostatin, insulin, and glucagon mRNA levels which occurs during the last 4 days of gestation [18].
• Gastrin biosynthesis involves a complex series of posttranslational modifications; their elucidation requires a knowledge of the structure of the gastrin precursor [20].
• Intracellular signal transduction during gastrin-induced histamine secretion in rat gastric ECL cells [21].

Anatomical context of Gast

• Bombesin dose-dependently increased gastrin secretion; this stimulatory effect on the G cell was significantly reduced after a 72-h starvation [6].
• BACKGROUND & AIMS: In gastric antrum, somatostatin exerts a tonic inhibitory influence on gastrin and histamine secretion [22].
• Gastrin is trophic for the normal gastric oxyntic mucosa and exerts a growth-promoting action on gastrointestinal malignancy [1].
• Thus, pancreatic gastrin gene expression shows a reciprocal relationship to the developmental expression of cholecystokinin in the duodenum [18].
• SOS, either alone or co-administered with epinephrine or gastrin heptadecapeptide (G17), dose-dependently stimulated SLI release by isolated canine fundic D-cells [23].

Associations of Gast with chemical compounds

• The aim of this study was to identify the sst subtype regulating gastrin and histamine secretion in human, dog, and rat stomach [22].
• The rate of gastrin release stimulated by carbachol was suppressed significantly by each dose of somatostatin examined (10(-8) M to 10(-4) M) [24].
• Basal and acetylcholine-stimulated gastrin release were significantly lower after a 3 day starvation, whereas the inhibitory effect of acetylcholine and the stimulatory effect of glucagon on somatostatin secretion were not influenced by fasting [6].
• Feeding did not change the sulfation of amidated heptadecapeptide gastrin or its glycine-extended variant [19].
• The post-translational processing of the pancreatic gastrin peptide, however, differs in being fully tyrosine sulfated, and thus it resembles gastrin's homologue, cholecystokinin [18].

Physical interactions of Gast

• These data suggest a SS receptor/G protein uncoupling as a result of binding of pentagastrin to gastrin receptors present in pancreatic acinar cell membranes [25].
• These new compounds bear a histamine H2 receptor antagonist (H2A) pharmacophore moiety attached to a gastrin receptor antagonist (GA) pharmacophore moiety in a reversed manner, namely the head-to-head manner, different from the previously reported head-to-tail manner [26].

Regulatory relationships of Gast

• Somatostatin inhibition of basal and carbachol-stimulated gastrin release in rat antral organ culture [24].
• Indeed, we observed a coprecipitation of both kinases and an inhibition of gastrin-induced PI 3-kinase activation when JAK2 activity is blocked [27].
• Gastrin enhances gastric mucosal integrity through cyclooxygenase-2 upregulation in rats [28].
• G17 induced p38 kinase activity at doses and with kinetics similar to those observed for Akt induction [29].
• To determine whether VDCCs contribute to histamine release stimulated by gastrin or pituitary adenylate cyclase-activating polypeptide (PACAP), the presence of VDCCs and their possible modulation by peptides was investigated in a 48-h cultured rat gastric cell population containing 85% ECL cells [30].

Other interactions of Gast

• Basal antral gastrin release was inhibited by somatostatin [24].
• We demonstrated that JAK2 functions as an upstream mediator of the phosphatidylinositol 3 (PI 3)-kinase activity in gastrin signaling [27].
• Pretreatment with nifedipine (10 microM), an L-type Ca2+ channel blocker, reduced PACAP-evoked pancreastatin secretion by 50-60%, gastrin-evoked secretion by approximately 80% and abolished the response to Bay K 8644 [31].
• Evaluation of the effects of pentagastrin, gastrin and pancreatic glucagon on cell proliferation in the rat gastrointestinal tract [32].
• We examined the action of G17 (10 nM) on phosphorylation and activation of protein kinase B/Akt, a kinase known to promote cell survival [29].

Analytical, diagnostic and therapeutic context of Gast

• Gastrin and histamine were measured by radioimmunoassay [22].
• Exogenous somatostatin given by intravenous infusion to conscious rats counteracted the release of gastrin stimulated by feeding, elevated antral pH or vagal excitation [33].
• G17 also induced FOXO3 phosphorylation assessed by Western blots with anti-phospho-FOXO3 antibodies, and BAPTA-AM inhibited this effect [3].
• In the current study, the actions of synthetic (sp) and native (np) porcine and synthetic human (sh) GIP, GLP-1(7-36), and GLP-1(7-37) on SLI and gastrin secretion were compared using a gradient perfusion of peptide [34].
• Mucus, gastrin and somatostatin cells in cultured rat antral mucosa: immunofluorescence, ultrastructural and radioimmunological studies [35].

1. Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor. Guo, Y.S., Cheng, J.Z., Jin, G.F., Gutkind, J.S., Hellmich, M.R., Townsend, C.M. J. Biol. Chem. (2002)
2. Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on the inhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells. Hofland, L.J., van Koetsveld, P.M., Waaijers, M., Zuyderwijk, J., Lamberts, S.W. Endocrinology (1994)
3. Intracellular mechanisms mediating the anti-apoptotic action of gastrin. Ramamoorthy, S., Stepan, V., Todisco, A. Biochem. Biophys. Res. Commun. (2004)
4. Hypogastrinemia in streptozotocin diabetes with islet transplantation--reconstitution. Fabri, P.J., Weber, C.J., Gower, W.R., Reemtsma, K. J. Surg. Res. (1983)
5. Effect of high temperature on gastrin, somatostatin and motilin production in ulcerous gastric antral mucosa of rats. Sun, F.P., Dan, H.L., Song, Y.G., Cheng, W. Di Yi Jun Yi Da Xue Xue Bao (2002)
6. Effect of food deprivation on rat gastric somatostatin and gastrin release. Koop, H., Schwab, E., Arnold, R., Creutzfeldt, W. Gastroenterology (1982)
7. Partial sleep deprivation compromises gastric mucosal integrity in rats. Guo, J.S., Chau, J.F., Cho, C.H., Koo, M.W. Life Sci. (2005)
8. Physiological role of cholecystokinin B/gastrin receptor in leptin secretion. Attoub, S., Levasseur, S., Buyse, M., Goïot, H., Laigneau, J.P., Moizo, L., Hervatin, F., Le Marchand-Brustel, Y., Lewin, J.M., Bado, A. Endocrinology (1999)
9. Serum gastrin increases with increasing dietary calcium but not with increasing dietary fat or fiber in Fischer-344 rats. Floor, M.K., Jahangeer, S., D'Ambrosio, C., Alabaster, O. J. Nutr. (1991)
10. Histamine in stress ulcer prophylaxis in rats. Warzecha, Z., Dembiński, A., Brzozowski, T., Ceranowicz, P., Dembiński, M., Stachura, J., Konturek, S.J. J. Physiol. Pharmacol. (2001)
11. Complete tyrosine-O-sulphation of gastrin in neonatal rat pancreas. Brand, S.J., Andersen, B.N., Rehfeld, J.F. Nature (1984)
12. GABA affects the release of gastrin and somatostatin from rat antral mucosa. Harty, R.F., Franklin, P.A. Nature (1983)
13. Localization of targets for anti-ulcer drugs in cells of the immune system. Mezey, E., Palkovits, M. Science (1992)
14. Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria. Brand, S.J., Stone, D. J. Clin. Invest. (1988)
15. Peptide YY inhibition of rat gastric enterochromaffin-like cell function. Zeng, N., Walsh, J.H., Kang, T., Wu, S.V., Sachs, G. Gastroenterology (1997)
16. Helicobacter pylori lipopolysaccharide stimulates histamine release and DNA synthesis in rat enterochromaffin-like cells. Kidd, M., Miu, K., Tang, L.H., Perez-Perez, G.I., Blaser, M.J., Sandor, A., Modlin, I.M. Gastroenterology (1997)
17. Influence of chronic drug-induced achlorhydria by substituted benzimidazoles on the endocrine stomach in rats. Koop, H., Willemer, S., Steinbach, F., Eissele, R., Tuch, K., Arnold, R. Gastroenterology (1987)
18. Differential gastrin gene expression in rat gastrointestinal tract and pancreas during neonatal development. Brand, S.J., Fuller, P.J. J. Biol. Chem. (1988)
19. Processing of the gastrin precursor. Modulation of phosphorylated, sulfated, and amidated products. Varro, A., Nemeth, J., Bridson, J., Lee, C., Moore, S., Dockray, G.J. J. Biol. Chem. (1990)
20. Molecular cloning and sequencing of a rat preprogastrin complementary deoxyribonucleic acid. Fuller, P.J., Stone, D.L., Brand, S.J. Mol. Endocrinol. (1987)
21. Intracellular signal transduction during gastrin-induced histamine secretion in rat gastric ECL cells. Zanner, R., Hapfelmeier, G., Gratzl, M., Prinz, C. Am. J. Physiol., Cell Physiol. (2002)
22. Somatostatin receptor subtype 2 mediates inhibition of gastrin and histamine secretion from human, dog, and rat antrum. Zaki, M., Harrington, L., McCuen, R., Coy, D.H., Arimura, A., Schubert, M.L. Gastroenterology (1996)
23. Sucrose octasulfate stimulates gastric somatostatin release. Lucey, M.R., Park, J., DelValle, J., Wang, L.D., Yamada, T. Am. J. Med. (1991)
24. Somatostatin inhibition of basal and carbachol-stimulated gastrin release in rat antral organ culture. Harty, R.F., Maico, D.G., McGuigan, J.E. Gastroenterology (1981)
25. The effect of pentagastrin on the somatostatin receptor/effector system in rat pancreatic acinar membranes. Alvaro-Alonso, I., Muñoz-Acedo, G., Arilla, E. Regul. Pept. (1994)
26. Synthesis and biological evaluation of a new reversely linked type of dual histamine H2 and gastrin receptor antagonist. Kawanishi, Y., Ishihara, S., Takahashi, K., Tsushima, T., Hagishita, S., Ishikawa, M., Ishihara, Y. Chem. Pharm. Bull. (1997)
27. Involvement of JAK2 upstream of the PI 3-kinase in cell-cell adhesion regulation by gastrin. Ferrand, A., Kowalski-Chauvel, A., Bertrand, C., Pradayrol, L., Fourmy, D., Dufresne, M., Seva, C. Exp. Cell Res. (2004)
28. Gastrin enhances gastric mucosal integrity through cyclooxygenase-2 upregulation in rats. Komori, M., Tsuji, S., Sun, W.H., Tsujii, M., Kawai, N., Yasumaru, M., Kakiuchi, Y., Kimura, A., Sasaki, Y., Higashiyama, S., Kawano, S., Hori, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2002)
29. Molecular mechanisms for the antiapoptotic action of gastrin. Todisco, A., Ramamoorthy, S., Witham, T., Pausawasdi, N., Srinivasan, S., Dickinson, C.J., Askari, F.K., Krametter, D. Am. J. Physiol. Gastrointest. Liver Physiol. (2001)
30. Role of neuropeptide-sensitive L-type Ca(2+) channels in histamine release in gastric enterochromaffin-like cells. Zeng, N., Athmann, C., Kang, T., Walsh, J.H., Sachs, G. Am. J. Physiol. (1999)
31. Somatostatin, misoprostol and galanin inhibit gastrin- and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca2+ channels. Björkqvist, M., Bernsand, M., Eliasson, L., Håkanson, R., Lindström, E. Regul. Pept. (2005)
32. Evaluation of the effects of pentagastrin, gastrin and pancreatic glucagon on cell proliferation in the rat gastrointestinal tract. Fatemi, S.H., Cullan, G.E., Sharp, J.G. Cell and tissue kinetics. (1984)
33. Topography of somatostatin cells in the stomach of the rat: possible functional significance. Alumets, J., Ekelund, M., El Munshid, H.A., Håkanson, R., Lorén, I., Sundler, F. Cell Tissue Res. (1979)
34. Gastric inhibitory polypeptide and glucagon-like peptide-1(7-36) amide exert similar effects on somatostatin secretion but opposite effects on gastrin secretion from the rat stomach. Jia, X., Brown, J.C., Kwok, Y.N., Pederson, R.A., McIntosh, C.H. Can. J. Physiol. Pharmacol. (1994)
35. Mucus, gastrin and somatostatin cells in cultured rat antral mucosa: immunofluorescence, ultrastructural and radioimmunological studies. Sahondramanarivo, G., Hollande, E., Pequignot, J., Accary, J.P., Dubrasquet, J.M. Gastroenterol. Clin. Biol. (1986)