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)

Serum gastrin and pancreatic secretion were measured in conscious Thomas fistula dogs during infusion of increasing doses of porcine gastrin, against a background of secretin. Dose-response relationships were calculated for the effects of gastrin on pancreatic secretion. Gastrin release was also measured after a test meal and after vagal stimulation with 2-deoxyglucose. Peak serum gastrin levels after these stimuli were less than the serum gastrin level associated with the minimal effective dose of gastrin. From the dose-response relationship of serum gastrin and pancreatic protein output, it was possible to calculate the protein output corresponding to the peak gastrin levels after 2-deoxyglucose or a meal. These were equivalent to 20-30% of the observed protein response to these stimuli. We conclude that gastrin plays at most a small part in the stimulation of pancreatic secretion after a meal and in response to 2-deoxyglucose. We also found that truncal vagotomy reduces pancreatic sensitivity to gastrin.
Pancreas 1987
PMID:Pancreatic responses to endogenous and exogenous gastrin in the dog. 362 29

To study the trophic effects of gastrin on the gastrointestinal tract, chronic endogenous hypergastrinemia was produced in rats by implantation of the gastric antrum into the colon. Rats were sham-operated (normal gastrin, normal acid) or were prepared with BII gastrojejunostomy and antral resection (low gastrin, low acid), or BII gastrojejunostomy and antral implantation into colon (high gastrin, acid present). To separate effects of hypergastrinemia from those of acid hypersecretion, two additional groups were prepared with total gastrectomy and either resection of the antrum (low gastrin, no acid) or antral implantation into colon (high gastrin, no acid). After 12 weeks, the pancreatic secretory response to secretin was measured. The animals were then sacrificed, and liver, pancreas, small intestine, and colon were weighed. In separate groups of animals villous height and width and crypt depth of small intestine and transverse colon were measured. Serum gastrin concentrations increased three- to fivefold in fasting and fed antral implant animals. Serum gastrin levels in the fed state were lower in antrectomy rats compared to controls but did not differ in the fasting rats. Pancreas and colon were heavier in all hypergastrinemic rats. Liver weights did not differ between hypergastrinemic animals and controls. Stimulated pancreatic bicarbonate secretion following secretin infusion was elevated only in hypergastrinemic, hyperacidic rats. Hypertrophy of the small bowel was seen in antral implant rats only when the gastric remnant was preserved (ie, when acid was present). Colonic mucosal thickness was increased in antral implant rats with or without gastrectomy. No significant increases in small-bowel villous height or crypt depth were found in antral implant rats. Thus, chronic endogenous hypergastrinemia caused pancreatic and colonic hypertrophy independent of acid secretion. In addition to hypergastrinemia, gastric hyperacidity was also needed for enlargement of small bowel or increase in secretin-stimulated pancreatic bicarbonate secretion.
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PMID:Effect of acid secretory capacity and chronic endogenous hypergastrinemia on pancreatic secretion and intestinal morphology in the rat. 682 82

Gastrin releasing peptide (GRP) immunoreactivity has been localized to nerve fibers innervating pancreatic acini and identified in nerve cell bodies within intrapancreatic ganglia. The role of intrapancreatic neurotransmission in GRP- and neuromedin C (NmC)-stimulated amylase release was investigated using rat pancreatic lobules in vitro. Lobule responsiveness to neuronal depolarization was demonstrated by amylase release upon exposure to 55 mM potassium (207 +/- 7% of control) or veratridine (294 +/- 12%). Both GRP and NmC produced dose-dependent increases in lobular amylase release, with ED50 values of 1.1 nM and 0.13 nM, respectively. Amylase release in response to submaximal concentrations of GRP were significantly inhibited by tetrodotoxin (78 +/- 5% of control) or hexamethonium (71 +/- 5% of control). GRP-stimulated amylase release was decreased to 71 +/- 5% of control by atropine coincubation. NmC-stimulated amylase release was not affected by tetrodotoxin, hexamethonium, or atropine. GRP (10(-10) to 10(-6) M) produced dose-dependent increments in [3H]acetylcholine release from pancreatic lobules. GRP stimulates amylase release from rat pancreatic lobules by a neurally mediated mechanism in addition to direct action on acinar membrane receptors.
Pancreas 1994 Jul
PMID:Gastrin-releasing peptide stimulation of amylase release from rat pancreatic lobules involves intrapancreatic neurons. 752 66

The short-chain pseudopeptide, [D-Phe6, Leu13 psi (CH2NH)Leu14]bombesin(6-14) (RDI), is reported to be a potent antagonist of bombesin, and development of this type of compound has greatly contributed to the investigation of biological actions of bombesin and its related peptides. We recently synthesized (E)-alkene bombesin isostere by replacing the peptide bond with an (E)-double bond: [D-Phe6, Leu13 psi [(E)CH = CH]Leu14] bombesin(6-14) (EABI). The present study examined the effect of EABI on amylase release from rat pancreatic acini. EABI showed no agonistic activity at concentrations up to 1 microM, and RBI showed slight agonistic activity at concentrations > 10 nM. EABI caused a dose-dependent inhibition of amylase release stimulated by 0.1 nM bombesin, with an IC50 of 6.7 +/- 1.7 nM, and induced almost-complete inhibition at 0.3 microM. RDI caused a dose-dependent inhibition of amylase release, with an IC50 of 68.7 +/- 16 nM. EABI caused a parallel and rightward shift of the entire dose-response curve of bombesin-stimulated amylase release, and the degree of the shift was dependent on the concentrations of EABI. EABI (100 nM) and RDI (100 nM) inhibited amylase releases stimulated by gastrin-releasing peptide (1 nM) and neuromedin-C (1 nM). In contrast, amylase release stimulated by cholecystokinin octapeptide (0.1 nM), carbachol (10 microM), vasoactive intestinal peptide (1 nM), and gastrin-17 (10 nM) was not inhibited by EABI and RDI. The results indicate that EABI is a potent and specific bombesin receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1995 Apr
PMID:Effect of a new bombesin receptor antagonist, (E)-alkene bombesin isostere, on amylase release from rat pancreatic acini. 754 72

The gastrointestinal peptide cholecystokinin (CCK) has been shown to stimulate pancreatic growth in the adolescent and adult rat. However, little is known about the role of gastrointestinal hormones in the regulation of organ formation during fetal development. We therefore examined the effects of the CCK receptor antagonist devazepide (25 micrograms/h) and an antigastrin/CCK monoclonal immunoglobulin G on the maternal and fetal rat pancreas. These substances were infused subcutaneously with minipumps in female rats during the entire period of gestation. At the end of gestation, the rats were killed and the pancreata of the dams and their litter were examined for DNA and protein. In the dams, the receptor antagonist and the antibody against CCK/gastrin had no effect. In the newborns, the CCK receptor antagonist led to a significant reduction of the protein and DNA concentration [protein in controls, 105.0 +/- 3.75 micrograms/mg pancreatic tissue; in the antagonist group, 91.9 +/- 4.2 micrograms/mg pancreatic tissue (p < 0.05); DNA in controls, 1.28 +/- 0.19 micrograms/mg pancreatic tissue; in the antagonist group, 0.48 +/- 0.06 micrograms/mg pancreatic tissue (p < 0.05) (mean +/- SEM)]. Immune neutralization of CCK/gastrin in the maternal-fetal circulation induced a reduction of the protein concentration in the fetal pancreas (85.3 +/- 3.06 micrograms/mg pancreatic tissue; p < 0.01) but had no effect on fetal pancreatic DNA. Additional experiments indicated effective concentrations of the CCK receptor antagonist in fetal pancreatic tissue and free binding sites of the circulating antibody. In conclusion, the study provides evidence that CCK and its analogues are involved in fetal pancreatic organogenesis.
Pancreas 1995 Apr
PMID:The role of CCK and its analogues in the organogenesis of the fetal rat pancreas. 762 5

The effect of partial hepatectomy (62 +/- 2% of liver mass) or sham laparotomy on the pancreas was studied in rats. Pancreatic contents of DNA, protein, and digestive enzymes were measured 14 days postoperatively. Pancreatic acini were prepared to study exocrine pancreatic function after hormonal stimulation. Islet hormone release was investigated in the isolated perfused pancreas. Liver regeneration reached 93 +/- 1% within 14 days. Water contents in liver and pancreas remained unaltered. Simultaneously, the pancreatic weight increased significantly. Pancreatic enzymes showed a parallel elevation, whereas DNA remained unaffected. Amylase secretion from pancreatic acini was unaltered. Stimulated insulin and somatostatin release from the perfused pancreas were both increased. Plasma cholecystokinin levels were elevated, whereas neurotensin was decreased. Insulin and gastrin remained unchanged. In conclusion, after partial hepatectomy, enhanced cholecystokinin and decreased neurotensin blood levels are suggested to contribute to a hypertrophic effect on the exocrine pancreas and an adaptive regulation of the endocrine gland.
Pancreas 1993 Mar
PMID:Partial hepatectomy affects pancreatic size and function in rats. 768 82

The clinical evolution of type I multiple endocrine neoplasia (MEN I) was studied in 45 patients among a consecutive series of 172 with Zollinger-Ellison syndrome (ZES). These 172 patients were seen in our hospital between 1959 and 1989. Diarrhea was half as frequent in ZES-MEN I as in sporadic ZES cases. At diagnosis, mean basal acid output and serum gastrin levels in MEN I patients (28.8 +/- 6.6 mmol/h and 587 +/- 487 pg/ml, respectively) were not different from those observed in the others with sporadic ZES. Laparotomy was performed in all 36 patients with no diffuse liver involvement to attempt the removal of gastrinomas. Twenty-nine patients had adenomas, located in the pancreas in 21, in the duodenal wall in 3, and in both in 5. Adenomas were multiple in 23 cases (78%). No tumor was found in seven patients. Twenty-nine of the 36 operated patients were tumor-free after surgery; 7 died in the postoperative period between 1959 and 1970. Median follow-up of the 38 other patients was 95 months (range 17-278 months). Among the 24 patients without residual tumor at discharge (group I), biological and/or morphological evidence of a persistent or recurrent source of gastrin was obtained in 22. Among the 14 patients with residual tumor (group II), an increase in tumor size was seen in 5 after a median of 27 months (range 9-36 months), while no change occurred in 9 after 54 months (3-100 months). Actuarial survival curves were not different, either in group I versus group II patients (67 and 72% at 5-year follow-up, respectively) or in MEN I versus sporadic ZES patients. Apparently, complete resection of primary tumor did not reduce the incidence of subsequent liver metastases. In all, 21 of the 45 patients had malignant gastrinomas (47%), consisting of liver metastases in 14 (31%), metastatic lymph nodes in 11 (24%), and lung metastases in 2 (4%). Monitoring of fundic argyrophil cells disclosed hyperplasia in 13 of the 14 MEN I patients (92%), and 5 had invasive carcinoid tumors. Taken together, these results prompt us to recommend that in ZES-MEN I patients, surgery should be avoided and oxyntic mucosa regularly monitored.
Pancreas 1993 May
PMID:Clinical, anatomical, and evolutive features of patients with the Zollinger-Ellison syndrome combined with type I multiple endocrine neoplasia. 809 74

In previous studies we found that duodenectomy abolished the interdigestive cycles of plasma motilin and pancreatic polypeptide (PP). In the current studies, we tested the hypothesis that an intact duodenopancreatic axis is necessary for normal postprandial release of pancreatic (PP, insulin) and gut peptides (gastric inhibitory peptide, GIP; cholecystokinin octapeptides, CCK-8; neurotensin; and gastrin). Consequently, we measured plasma concentration of pancreatic and gut hormones in normal and duodenectomized dogs after gavage feeding of a 250-ml liquid formula diet in conscious animals. After completing the experiments, pancreatic tissue concentrations of PP and insulin were measured. Removal of the duodenum was associated with decreases in postprandial plasma concentrations of PP (p < 0.05) and insulin (p < 0.05) and in pancreatic tissue concentrations of insulin (p = 0.01). Duodenectomy, however, did not alter postprandial plasma concentrations of GIP, CCK-8, neurotensin, or gastrin nor pancreatic tissue concentrations of PP. These effects of duodenectomy may be due to disruption of duodenopancreatic neural connections or loss of vagus sensitive (non-GIP) humoral factors. Decreased postprandial insulin concentrations may be due to lack of a neural or humoral insulinotropic factor arising from the duodenum.
Pancreas 1994 Jan
PMID:Role of the duodenum in postprandial release of pancreatic and gastrointestinal hormones. 810 66

Cholecystokinin (CCK-A) and gastrin (CCK-B) receptors have been demonstrated in the azaserine-induced rat pancreatic carcinoma DSL-6. In order to determine at what stage in azaserine-induced pancreatic carcinogenesis gastrin (CCK-B) receptors are first expressed, we examined the binding of [125I]gastrin-I to normal rat pancreas, azaserine-induced premalignant pancreatic nodules, grossly normal internodular pancreas, and DSL-6 carcinoma. We observed that specific gastrin binding was absent in normal pancreas, premalignant nodules, and internodular pancreas, and also reconfirmed our previous report of marked overexpression of gastrin (CCK-B) receptors in the DSL-6 carcinoma. Specific cholecystokinin (CCK) binding was present in all pancreatic tissue types tested. Therefore, we conclude that the presence of gastrin (CCK-B) receptors in the azaserine-induced pancreatic carcinoma DSL-6, in contrast to their absence in premalignant nodules, suggests that the expression of the gastrin (CCK-B) receptor may be important in the transformation from premalignant nodules to pancreatic cancer.
Pancreas 1993 Sep
PMID:Temporal expression of the gastrin (CCK-B) receptor during azaserine-induced pancreatic carcinogenesis. 830 99

Gastrin releasing peptide (GRP) is known to stimulate pancreatic enzyme and islet hormone secretion. In the present immunohistochemical study, the localization and distribution of GRP-like immunoreactivity were investigated in the human pancreas using two antisera with different specificities. GRP-like immunoreactivity (GRP-LI) was observed in numerous nerve fibers diffusely distributed to the exocrine pancreas, but was not seen in intrapancreatic nerve cells of normal pancreatic specimens examined. Nerve fibers and terminals with GRP-LI were found in abundance around pancreatic acini and capillaries, with moderate density around ductules and in the walls of arterioles, and a few were seen in islets. This distribution pattern was quite similar to that of vasoactive intestinal polypeptide (VIP)-LI nerve fibers. The study, using the antibody elution method, strongly suggests the co-localization of GRP- and VIP-LIs within a part of VIP-containing nerve fibers. In the chronic pancreatitis specimens, neurons with GRP-LI were frequently found, and > 90% of intrapancreatic nerve cells were VIP-immunoreactive. Immunostainings for GRP and for VIP on serial adjacent sections of intrapancreatic ganglia from chronic pancreatitis specimens suggested the co-localization of the two immunoreactivities in > 70% of intrapancreatic neurons. The present findings may provide a morphological basis for neurotransmitter and/or neuromodulator roles of GRP in the human pancreas.
Pancreas 1993 Jul
PMID:Neurons containing gastrin releasing peptide-like immunoreactivity in the human pancreas. 836 58


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