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

The neuropeptide bombesin has been shown to stimulate secretion of several gastrointestinal hormones, including cholecystokinin (CCK). We have previously demonstrated that stimulation of CCK release by feeding is associated with an increase in steady-state intestinal CCK mRNA levels. The purpose of the present study was to determine whether bombesin stimulates CCK release in rats and, if so, to determine whether bombesin regulates CCK mRNA levels in a manner similar to that of feeding. To establish a proper dose of bombesin for stimulating CCK release, rats received 1-h intravenous infusions of 0.25, 1, 4, or 16 micrograms.kg-1.h-1 bombesin. Basal plasma CCK levels averaged 1.8 +/- 0.4 pM and increased to peak levels of 2.9 +/- 0.6 pM within 15 min of infusion with 4 micrograms.kg-1.h-1 bombesin (the maximally effective dose). With the use of this dose, rats then received infusions of bombesin or saline lasting up to 24 h. At 1, 2, 4, and 24 h, animals were killed for collection of plasma for CCK measurements and of intestine for measurements of intestinal CCK and somatostatin mRNA levels. Bombesin treatment stimulated an increase in plasma CCK levels at 1 h, but levels declined to basal by 4 h, where they remained at 24 h. Despite increasing plasma CCK levels, bombesin infusion, unlike dietary stimulation, had no effect on duodenal CCK mRNA levels. Finally, to determine whether the decrease in plasma CCK levels after prolonged bombesin treatment was due to tachyphylaxis, rats treated with bombesin for 4 h were also fed soybean trypsin inhibitor (a known stimulus of CCK secretion).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of intestinal cholecystokinin and somatostatin mRNA by bombesin in rats. 167 36

The endocrine cells of the chicken proventriculus were investigated immunocytochemically, using the peroxidase-antiperoxidase technique on paraffin and semithin sections for light microscopy, and immunogold staining in osmium-fixed material for electron microscopy. The fixation procedure also allowed a detailed ultrastructural investigation. Twenty-three antisera were tested and 7 immunoreactive cell-types were identified: D-cells containing somatostatin-like peptide; EG-cells immunoreactive to anti-glucagon, anti-GLP1 and anti-neurotensin; NT-cells labelled only with anti-neurotensin; BN-cells containing bombesin-like material; ENK-cells showing met-enkephalin immunoreactivity; EC-cells reactive to anti-serotonin; and APP-cells positive to anti-avian pancreatic polypeptide. In addition, enterochromaffin-like (ECL) cells, were also detected by electron microscopy. The presence of ENK-cells and the ultrastructure of these and NT-cells are described for the first time in chicken proventriculus, and glucagon. GLP1 and neurotensin are shown to be colocalized in the EG-cells.
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PMID:Immunocytochemical and ultrastructural characterization of endocrine cells in chicken proventriculus. 167 89

Several neuropeptides known to alter gastrointestinal motility are present in milk. We investigated the effect of gastric administration of neurotensin, bombesin, somatostatin, and vasoactive intestinal polypeptide on gastrointestinal motility in suckling rats. We gavage fed 7- to 10-day-old rats with a meal consisting of 10 microliters/g of body weight of 0.9% NaCl with 51Cr tracer and one of the peptides (0, 0.1, 10, and 1,000 ng/ml). We estimated the rates of gastric emptying and the small intestinal transit from the distribution of the radioactivity in the gut. Approximately one-half of the counts emptied from the stomach in 15 min. Both gastric emptying and small intestinal transit were time dependent and were accelerated by metoclopramide and inhibited by butylscopolamine. Neurotensin 1 micrograms/ml accelerated the gastric emptying by 35% (p less than 0.02). Small intestinal transit was also accelerated (p less than 0.05). The other neuropeptides had no effect on gastric emptying and small intestinal transit. Neurotensin did not change either the gastric emptying or small intestinal transit in weaned rats, 40-50 days old, studied in the same manner. These data suggest that the intraluminal administration of neurotensin may increase gastrointestinal motility in suckling animals.
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PMID:Oral neurotensin increases gastrointestinal transit in suckling rats. 168 Oct 45

Female Syrian golden hamsters with N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancers were treated for 2 months with new pseudononapeptide bombesin receptor antagonist [D-Tpi6,Leu13 psi (CH2NH)-Leu14]bombesin(6-14)(RC-3095), administered s.c. with implanted osmotic minipumps releasing 20 micrograms/day of the analogue. The results were compared to those obtained by treatment with somatostatin analogue RC-160 (35 micrograms/day and 150 micrograms/day) or [D-Trp6]luteinizing hormone-releasing hormone (25 micrograms/day), which inhibited the growth of pancreatic cancers in our previous studies. A new acetylated somatostatin analogue [formula: see text] (30 micrograms/day) also was used for comparison of therapeutic response. All peptide analogues induced tumor inhibition by at least one of the measured parameters. Bombesin antagonist RC-3095 and high dose of RC-160 (150 micrograms/day) had the greatest inhibitory effect on pancreatic cancers: A significant decrease in the number of animals with tumors, reduced pancreatic weight, 87-89% inhibition of tumorous pancreas weight, and a significant diminution in the number of tumor nodules and argyrophilic nucleolar organizer region count in tumor cell nuclei were observed in the groups treated with these regimens. We were able to detect receptors for bombesin in membranes of N-nitrosobis(2-oxopropyl)amine-induced pancreatic tumors and these receptors were not down-regulated after treatment with the bombesin antagonist. In hamsters treated with bombesin antagonists, tumor inhibition might be explained by a significant decrease in the binding capacity of epidermal growth factor receptors in pancreatic cancers. The acetylated somatostatin analogue RC-160-II had a similar inhibitory effect on the tumors as the original analogue RC-160. Our results suggest that the increase in the dose of RC-160 improves the therapeutic response, and this finding should be taken into account in clinical use of this somatostatin analogue. In view of its strong inhibitory effect on experimental pancreatic tumors, the bombesin antagonist RC-3095 might be considered as a possible new agent for the therapy of human exocrine pancreatic cancer.
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PMID:Inhibitory effect of bombesin/gastrin-releasing peptide antagonist RC-3095 and high dose of somatostatin analogue RC-160 on nitrosamine-induced pancreatic cancers in hamsters. 168 39

Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with a [D-Trp6] agonist of luteinizing hormone releasing hormone (LH-RH), somatostatin analogue (RC-160), and bombesin/gastrin releasing peptide antagonist (RC-3095). Some inhibitory effect of [D-Trp6] LH-RH microcapsules releasing 25 micrograms/day on tumor growth was observed that could be due to sex steroid deprivation, but the inhibition was not statistically significant. Microcapsules of RC-160, releasing 50 micrograms/day, significantly reduced tumor volume after 21 and 24 days of treatment, but at the end of the experiment the inhibition in tumor volume and weight was not significant. Bombesin/gastrin releasing peptide antagonist RC-3095, at a dose of 20 micrograms/day administered by daily s.c. injections or by continuous infusion using Alzet osmotic minipumps, had the greatest inhibitory effect on tumor growth. Tumor volume, percentage change in tumor volume, and tumor weights were significantly decreased in both groups treated with RC-3095. This is the first report on inhibition of human colon cancer growth in vivo by bombesin antagonists.
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PMID:Inhibition of growth of HT-29 human colon cancer xenografts in nude mice by treatment with bombesin/gastrin releasing peptide antagonist (RC-3095). 168 40

The mechanism of action of bombesin, also known as gastrin-releasing peptide (GRP), on somatostatin secretion was examined separately in superfused segments of rat antral and fundic mucosa. Bombesin/GRP (1 nM) stimulated somatostatin secretion from both regions. In fundic segments, the somatostatin response was strongly inhibited (86%; P less than 0.01) by tetrodotoxin (5 microM) but augmented by atropine (1 microM) (P less than 0.01). In antral segments, both tetrodotoxin and atropine augmented the somatostatin response to bombesin/GRP by 42-45% (P less than 0.01), whereas the gastrin antagonist L 365260 (1 microM) abolished it. The gastrin antagonist augmented the gastrin response to bombesin/GRP by 103% (P less than 0.01). The results indicate that bombesin/GRP stimulates somatostatin secretion by distinct mechanisms in the fundus and antrum. In the fundus, bombesin/GRP acts indirectly on somatostatin cells by activating stimulatory noncholinergic neurons and, to a lesser extent, inhibitory cholinergic neurons. In the antrum, bombesin/GRP acts indirectly on somatostatin cells by stimulating release of gastrin and, to a lesser extent, by activating inhibitory cholinergic neurons. A dual paracrine pathway links gastrin and somatostatin secretion in the antrum.
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PMID:Bombesin/GRP-stimulated somatostatin secretion is mediated by gastrin in the antrum and intrinsic neurons in the fundus. 168 68

Endocrine cells in the gastrointestinal tract of the domestic duck were identified immunocytochemically using antisera specific to bombesin, chromogranin A, cholecystokinin (CCK), gastrin, glucagon, neuron specific enolase (NSE), neurotensin, secretin, 5-hydroxytryptamine (5-HT), somatostatin, substance P and vasoactive intestinal polypeptide (VIP). Chromogranin A, 5-HT and somatostatin immunoreactive cells were widespread throughout the gastrointestinal tract. Bombesin immunoreactive cells were observed only in the proventriculus and the gizzard. CCK, substance P and neurotensin immunoreactive cells were present in the intestinal tracts from the duodenum to the colorectum. The latter were numerous also in the antrum. Gastrin cells were peculiar to the antrum but present also in the gizzard and small intestine. Glucagon immunoreactive cells were present in the jejunum-ileum and above all in the large intestine. Only few secretin cells were present in the duodenum. The highest frequency of endocrine cells was found in the antrum, while the lowest was observed in the caeca. Antisera to somatostatin and substance P showed numerous nerve cells and fibers besides endocrine cells, whereas NSE and VIP immunopositivity was found in the nervous structures only of the gut wall.
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PMID:An immunohistochemical study on the endocrine cells in the gastrointestinal tract of domestic duck. 168 96

Intact segments of rat ileum were stimulated in vitro by either electrical field stimulation (EFS) or cholinergic stimulation with carbachol, in the presence of absence of varying insulin concentrations (50, 100 and 200 microU/ml), and the contraction in the longitudinal axis was recorded. Insulin had no significant influence on the carbachol contractile dose-response curve nor did it affect the cholinergically mediated 'on-contraction' at onset of the electrical stimulus. The 'off-contraction' occurring at cessation of the electrical stimulus was partly mediated by a cholinergic and partly by a noncholinergic and nonadrenergic mechanism, and decreased over time with repeated stimulation. This decay with time was significantly attenuated by insulin. In the presence of insulin, release of bombesin-like immunoreactivity induced by carbachol or EFS significantly increased. On the other hand, the release of somatostatin-like immunoreactivity was suppressed by 50-70% in the presence of insulin. These results demonstrate that in vitro insulin can modify both the motility responses of isolated segments of rat ileum and the neuropeptide release from such segments.
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PMID:Modulatory effect of insulin on rat small intestinal motility and peptide release in vitro. 168 70

The major determinant of meal-stimulated gastric acid secretion is the antral hormone gastrin. Decarboxylated amine derivatives of amino acids have been proposed as the final common mediators of gastrin secretion stimulated by a meal. We explored the cellular basis for this hypothesis using a recently developed isolated canine G-cell model. Both amino acids and, more potently, their corresponding amines, directly stimulated gastrin release. Amino acid-stimulated gastrin secretion was unaffected by decarboxylase inhibitors (alpha methyldopa, aminooxyacetic acid, and 4-deoxypyridoxine) but enhanced by bombesin, isobutylmethylxanthine, and dibutyryl cAMP. Somatostatin inhibited amino acid-stimulated gastrin release via a pertussis toxin-sensitive GTP-binding protein. In contrast, gastrin secretion induced by amines was unaltered by any of the various treatments. Our data indicate that amino acids and amines, either as primary constituents of an ingested meal or as metabolites of dietary proteins, act directly via separate mechanisms to stimulate gastrin secretion from G-cells.
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PMID:Amino acids and amines stimulate gastrin release from canine antral G-cells via different pathways. 168 66

The effects of bombesin on the growth of the gastroduodenal mucosa and the pancreas have been examined in adult rats with intact or resected antrum and following administration of somatostatin or CCK-receptor antagonist L-364,718. The peptides were administered three times daily for 7 consecutive days, and then the animals were sacrificed and growth parameters (organ weight and RNA and DNA contents) were determined, and plasma gastrin and CCK were assayed. Compared with the control (saline) values, bombesin significantly stimulated the growth of the oxyntic and duodenal mucosa and the pancreas. These effects were partly reduced but not abolished by somatostatin, antrectomy and L-364,718, suggesting that bombesin may enhance the growth partly by releasing gastrin and CCK and partly by direct action on these tissues.
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PMID:Role of gastrin and cholecystokinin in the growth-promoting action of bombesin on the gastroduodenal mucosa and the pancreas. 169 18


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