Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rat pancreatic cell line, AR42J possessed high-affinity gastrin and somatostatin receptors and its growth was stimulated by physiological gastrin-17 concentrations between 5 x 10(-11) mol/l and 10(-9) mol/l as measured by [75Se]selenomethionine uptake. The somatostatin analogue, octreotide (2 x 10(-7) to 2 x 10(-11) mol/l), reduced this stimulated growth. Gastrin-stimulated AR42J growth was also inhibited by proglumide (3 x 10(-4) mol/l) and lorglumide (3 x 10(-5) mol/l) at maximal G17 concentrations of 5 x 10(-11) and 10(-10) mol/l, respectively, and the analogues competed with [125I] gastrin-17 (5 x 10(-10) mol/l) for binding to gastrin receptors on AR42J (50% inhibitory concentrations, less than or equal to 10(-3) mol/l and 4 x 10(-6) mol/l, respectively. Octreotide reduced the basal growth of the human gastric cell line, MKN45G, (which is associated with intracellular gastrin immunoreactivity) in serum-free medium to 73% of control at a concentration of 2 x 10(-8) mol/l, which was reversed by gastrin-17 (10(-10) mol/l). Lorglumide (3 x 10(-5) mol/l) also reduced the basal growth to 30% of control, which was reversed to 78% by 10(-5) mol/l gastrin. Proglumide had no effect on the basal growth of MKN45G.
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PMID:Inhibition of gastrin-stimulated growth of gastrointestinal tumour cells by octreotide and the gastrin/cholecystokinin receptor antagonists, proglumide and lorglumide. 135 50

In the present study we have investigated the effects of proglumide (PRO) and somatostatin analog (SMS 201-995) on the mitotic activity of colonic mucosa in rats under basal conditions and after omeprazole (OM). The stathmokinetic method was used. Proglumide and OM were administered for 5 days, twice daily, SMS 201-995 on the 5th day of the experiment only, also twice daily. It was found that: 1) OM enhanced the proliferation of colonic mucosa, as well as increased serum gastrin, when compared to controls, 2) OM and PRO, when applied jointly, decreased the mitotic activity of the colonic epithelium, 3) PRO alone increased the colonic cell proliferation.
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PMID:Effect of omeprazole-induced hypergastrinaemia on the proliferation of colonic mucosal epithelial cells in the rat. 186 13

The effects of gastrin, proglumide (a gastrin receptor antagonist), and somatostatin on growth of human colon adenocarcinoma cell lines CX1, X56, and HT29 were examined in two experimental models. Nude mice bearing xenografts of colon cancer CX1 or X56 were treated for 14-25 days subcutaneously with saline, pentagastrin (0.5 or 1.0 mg/kg), proglumide (250 or 500 mg/kg), or somatostatin 14 (33, 100, or 300 micrograms/kg) twice daily. Tumor volume, weight, protein, and deoxyribonucleic acid were measured. HT29 cells were grown in vitro and the effects of gastrin 17, proglumide, and somatostatin on growth were evaluated by cell counts or [3H]thymidine incorporation. The larger dose of pentagastrin significantly increased tumor growth in the nude mouse (p less than 0.005) and gastrin induced a biphasic effect on deoxyribonucleic acid synthesis in tissue culture with significant increases of up to 39% (p less than 0.025). Somatostatin alone significantly inhibited tumor growth in two of the cell lines and also inhibited the gastrin-induced growth. Proglumide had no effect by itself but significantly inhibited gastrin-stimulated growth. These findings suggest that growth of some human colon cancers may be hormone-dependent.
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PMID:Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer. 290 11

The cellular localization of gastrin receptors was studied using dispersed canine fundic mucosal cells. In previous studies 125I-[Leu15]gastrin-17 (125I-[Leu15]G-17) binding was found to parietal cells, but gastrin binding was also found in the small-cell elutriator fractions (SCEF). In the present study a density gradient was used to further separate the SCEF and the distribution of 125I-[Leu15]G-17 binding correlated with cellular content of somatostatinlike immunoreactivity (SLI). In contrast, 125I-[Leu15]G-17 binding was inversely correlated with the histamine content of the fractions. 125I-[Leu15]G-17 binding to the SCEF was rapid and reversible. Total binding was 0.29 +/- 0.02 fmol/10(6) cells (mean +/- SE, n = 15); excess unlabeled G-17 inhibited 85% of this binding. G-17, [Leu15]G-17, and 127I-[Leu15]G-17 were equipotent in inhibiting 125I-[Leu15]G-17 binding and stimulating SLI secretion from the SCEF placed in short-term culture, whereas 127I-G-17 had a low potency for both effects. Proglumide, known to inhibit cholecystokinin binding to pancreatic acinar cell receptors, also inhibited 125I-[Leu15]G-17 binding to the SCEF and inhibited G-17 stimulated SLI release. We conclude that in the canine fundic mucosa gastrin interacts with receptor sites on parietal cells and somatostatin cells but probably not on fundic mucosal histamine-containing cells. These receptor sites for gastrin may activate counterbalancing mechanisms regulating the secretion of acid.
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PMID:Gastrin receptors on nonparietal cells isolated from canine fundic mucosa. 609 79

An intraperitoneal (i.p.) injection of pentagastrin (250 micrograms/kg, three times daily) for 1 week increased somatostatin like-immunoreactivity (SSLI) content in the pancreas and the number of somatostatin (SS) receptors in pancreatic acinar membranes without influencing their apparent affinity as compared with control animals. No significant differences were seen in basal or forskolin (FK)-stimulated adenylate cyclase (AC) enzyme activities in the control and pentagastrin treated rats. In spite of the increase in the number of SS receptors, SS caused a significantly lower inhibition in AC activity in these membranes. This finding is related to the fact that the stable GTP analogue, 5'-guanylylimidodiphosphate (Gpp[NH]p) was a much less potent inhibitor of binding in the pancreatic acinar cell membranes from pentagastrin-treated animals than in those from controls. In addition the ability of Gpp(NH)p to inhibit FK-stimulated AC activity was also decreased in pancreatic acinar cell membranes from pentagastrin-treated rats. Pretreatment with proglumide, (20 mg/kg i.p.) a gastrin/cholecystokinin (CCK) receptor antagonist, prevented the pentagastrin-induced changes in SS level and binding as well as the inhibitory effect of SS on AC activity in pancreatic acinar cell membranes. Proglumide alone had no observable effect on the somatostatinergic system. 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.
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PMID:The effect of pentagastrin on the somatostatin receptor/effector system in rat pancreatic acinar membranes. 771 80

The mechanism whereby somatostatin (SS) produces beneficial effects in established pancreatitis induced by pancreaticobiliary duct ligation (PBDL) is still not clear. The aim of the work was to evaluate the possibility of a direct action of SS on pancreatic acinar cells from rats with acute pancreatitis. For this purpose, we studied the SS-receptor-adenylate cyclase system in pancreatic acinar membranes from both, control rats and rats with experimentally induced acute pancreatitis. On the other hand, it has been reported that cholecystokinin (CCK) diminishes the number of SS receptors in pancreatic acinar cells. Proglumide, a CCK receptor antagonist reduces the severity of acute pancreatitis in the rat. Therefore, we have also examined the effect of proglumide on the somatostatinergic system in controls and rats with acute pancreatitis. Fourteen hours after PBDL, the SS receptors, the capacity of the SS analogue SMS 201-995 to inhibit forskolin-stimulated adenylate cyclase activity and PTX-catalyzed [32P] ADP-ribosylation of the alpha1 subunits of Gi proteins could not be detected in pancreatic acinar membranes. One month after reopening the closed pancreaticobiliary duct (PBD), the pancreas showed regeneration of acinar cells, and the above-mentioned parameters were significantly lower than in the control group. Two months after reopening the closed PBD, all these parameters had returned to control values. The administration of proglumide (20 mg/kg i.p.), a cholecystokinin receptor antagonist, accelerated pancreatic regeneration and approached all these parameters to control values one month after reopening the closed PBD. The present study suggests that the beneficial effects of SS on established pancreatitis induced by PBDL may not be due to a direct action of the peptide on pancreatic acinar cells at least at 14 hours after PBDL. In addition, these findings suggest that in established pancreatitis the effect of proglumide on the SS receptor-adenylate cyclase system could be due to its action on pancreatic regeneration.
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PMID:The somatostatin receptor-adenylate cyclase system in rat pancreatic acinar membranes after temporary pancreaticobiliary duct ligation. 940 49