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)

Pancreastatin is a peptide isolated from the porcine pancreas and shown to inhibit insulin release. We have studied the immunocytochemical distribution of pancreastatin in three porcine endocrine tissues: pancreas, gut, and adenohypophysis. Pancreastatin-specific immunoreactivity was found in all three locations and distributed to numerous cells. In the pancreas, we performed the alternate labeling of consecutive thick (immunofluorescence) or thin (protein A-gold) sections and we observed that pancreastatin colocalizes to secretory granules of insulin and somatostatin-containing cells. The relationship of pancreastatin to chromogranin A is discussed.
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PMID:Localization of pancreastatin immunoreactivity in porcine endocrine cells. 289 59

Pancreastatin is a recently identified 49-amino-acid peptide found in gastrointestinal tract and gastric mucosa. Its biologic effects on gastric function are unknown. The aim of this study was to determine the effects of pancreastatin [33-49] (the synthetic C-terminal fragment) on acid secretion and somatostatin release in vitro. Isolated rabbit gastric glands were prepared by means of collagenase digestion. Acid secretion was assessed indirectly with use of 14C-aminopyrine (AP) uptake by glands, and somatostatin release from D cells was measured with radioimmunoassay. Pancreastatin alone (10(-10) to 10(-6) mol/L) had no effect on 14C-AP uptake compared with unstimulated glands. In contrast, pancreastatin inhibited with histamine-(10(-6), 10(-5) mol/L; p less than 0.005) and carbachol-(10(-5), 10(-4) mol/L; p less than 0.001) stimulated 14C-AP uptake in a dose-dependent manner. Neither forskolin-(10(-6), 10(-4) mol/L; p greater than 0.50) or 8-Br-cAMP-(10(-5), 10(-4) mol/L; p greater than 0.30) stimulated 14C-AP uptake were influenced by pancreastatin. Pancreastatin had no effect on somatostatin release from glands. These data suggest that pancreastatin probably acts at receptor or membrane level, inhibiting both histamine- and carbachol-stimulated 14C-AP uptake. These effects are not mediated by D cell somatostatin release. It is possible that pancreastatin acts as a paracrine or endocrine inhibitory regulator of parietal cell secretion.
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PMID:Pancreastatin: a novel peptide inhibitor of parietal cell secretion. 290 81

For various pituitary adenomas, it has been demonstrated that somatostatin receptor can be present. Pilot studies have shown that radio-indium labeled pentetreotide allows very good scintigraphic localization of somatostatin receptor-bearing cell masses. Recently, the presence of CgA in pituitary adenomas has also been demonstrated. MAb A11, raised against CgA, has been successfully used with a three-step ISG for the diagnosis of neuroendocrine tumors. Therefore the combined use of three-step ISG with MAb A11 and radiolabeled somatostatin can be useful in the diagnosis of pituitary adenomas. Twelve patients, 5 secreting (group A) and 7 nonsecreting (group B) pituitary adenomas, were enrolled in the study. All patients underwent three-step ISG, and, 2 wk later, scintigraphy with 111In-labeled pentetreotide (Octreoscan). Three-step ISG consisted of i.v. injection of 1 mg of biotinylated MAb A11 (first step), followed by 10 mg of avidin (second step) and [99mTc]PnAO-biotin (third step). Tomographic imaging were acquired for three-step ISG and Octreoscan at 2 and 4 h after radiotracer injection, respectively. The results are the following: 2 patients of group A (secreting tumors) had a positive three-step ISG, whereas all the patients but one of the same group had a positive pentetreotide study; all the patients of group B (nonsecreting tumors) had a positive three-step ISG and 4 had a positive pentetreotide scintigraphy. These data suggest the utility of the combined use of these techniques for a better diagnosis of pituitary adenomas.
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PMID:Combined use of 111In-labeled pentetreotide and three-step immunoscintigraphy with antichromogranin A monoclonal antibody in the diagnosis of pituitary adenomas. 773 36

The effects of long term (6-month), high (500-micrograms), once a day administration of octreotide on enterochromaffin-like (ECL) cell proliferation were evaluated in eight patients with hypergastrinemic atrophic gastritis at risk for the development of gastric carcinoids. Fasting gastrin levels were determined during treatment and up to 6 months after the end of treatment. Chromogranin A, hCG alpha, and somatostatin-immunostained cells were morphometrically evaluated in biopsy specimens of corpus mucosa taken before and after treatment. The results showed that gastrin levels significantly decreased from 950 to 238 ng/L (-74.9%; P < 0.01) at the end of treatment, a decrease that persisted 6 months after the end of treatment (450 ng/L; P < 0.05). The volume density of CgA cells (mostly ECL cells) decreased from 3.7% to 2.1% of the epithelial component (-43%; P < 0.014), that of hCG alpha-storing ECL cells decreased by 85% (P < 0.0007), and that of somatostatin-stained cells decreased by 74% (P < 0.04). No clinically significant side-effects were found. It is concluded that octreotide treatment as used in the present study is safe and effective in reducing hypergastrinemia and associated ECL cell changes in patients with atrophic gastritis. The decrease in D cells is consistent with the occurrence of somatostatin receptors and related autocrine regulation in these cells.
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PMID:Effectiveness of octreotide in controlling fasting hypergastrinemia and related enterochromaffin-like cell growth. 863 88

Pancreastatin (PST) is known to inhibit glucose-stimulated insulin release both in vivo and in vitro, but it has not been determined whether PST acts directly on pancreatic B-cells and no study has been reported on the effect of PST on the intracellular free Ca2+ concentration ([Ca2+]i) in pancreatic islet cells. In the present study, by using the dissociated rat pancreatic B-cells, we examined the effects of PST on the increase in [Ca2+]i induced by several insulin secretagogues, and compared them with those of somatostatin (SRIF). PST (1-100 nM) dose-dependently inhibited the glucose-induced rise in [Ca2+]i in single pancreatic islet cells. SRIF (10 nM) also suppressed the glucose-induced rise in [Ca2+]i. These demonstrated direct inhibitory actions of PST and SRIF on the pancreatic B-cells. Acetylcholine (ACh, 10 microM) with 5.5 mM glucose induced a biphasic increase in [Ca2+]i in single islet cells. SRIF (10 nM) suppressed the second phase in [Ca2+]i increase without affecting the first phase. In contrast, PST (100 nM) had no effect on the ACh-induced response. Gastric inhibitory polypeptide (100 nM) with 5.5 mM glucose induced a rise in [Ca2+]i in single islet cells. SRIF inhibited this increase, but PST did not. Both PST and SRIF failed to affect the sustained rise in [Ca2+]i evoked by excess K+. These results suggest that PST and SRIF suppress the glucose-induced insulin secretion at least partly by inhibiting the rise in [Ca2+]i in pancreatic B-cells. Furthermore, PST may suppress the glucose-induced rise in [Ca2+]i via a mechanism different from that of SRIF.
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PMID:Effects of pancreastatin and somatostatin on secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells. 885 17

N-terminal chromogranin A (CGA) contains peptides with vasoinhibitory properties, called vasostatin I (VST) and II [CGA (1-76) and (1-113) in human and bovine; (1-128) in rat]. Three fragments of VST were synthesized and antisera raised: human CGA (68-76) (VST I) rat CGA (121-128) (VST II fragment 2), and bovine/human CGA (83-91) (VST II, fragment 3). Strong immunoreactivity was observed in PC12 cells with antisera to VST II, fragment 3, VST I, and neuron-specific enolase. Little or no immunoreactivity was observed using antisera to synaptophysin, whole molecule CGA, pancreastatin, protein gene product 9.5, somatostatin, pancreatic polypeptide, or with antibodies 875 and 876 to VST II, fragment 2. Most of the VST antisera cross-reacted, with a species of molecular weight, 61 kDa but one, 874, cross-reacted with two species of molecular weights, 7.2 and 12 kDa. Our results show the presence of N-terminally processed CGA in PC12 cells.
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PMID:PC12 cells show immunoreactivity to a number of proteins and peptides, including vasostatin. 897 22

The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted throughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.
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PMID:An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei). 900 19

Co-localization of chromogranin (Cg) A, B, and C has been studied in different neuroendocrine cell types in histologically normal mucosa from human gastrointestinal tract (corpus, antrum, duodenum, ileum, and colon) using single-, double-, and triple-immunofluorescence stainings. Virtually all enterochromaffin (EC) cells contained CgA, and those in the luminal two thirds of the antral mucosa and villi of small intestine often also contained CgB. A few EC cells in the duodenal crypts contained CgC. Most gastrin cells harbored both CgB and CgA, although rather more CgB than CgA, but some gastrin cells contained all three types, i.e., also CgC. Some CCK cells also contained all three chromogranins. Enteroglucagon cells in the duodenal villi contained CgA and some CgB. CgA (but not B or C) was found in some secretin, GIP, enteroglucagon/peptide YY, and neurotensin cells. A few somatostatin cells contained CgA but neither CgB nor CgC. CgA and C were found mainly in the basal cell region, whereas CgB occurred more diffusely throughout the cytoplasm. This varying distribution suggests that not all secretory granules contain CgA, or that CgB may occur in a nongranular form. The varying composition of the different chromogranins may reflect their complex functional roles in the widespread neuroendocrine system.
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PMID:Complex co-localization of chromogranins and neurohormones in the human gastrointestinal tract. 919 67

The stimulus-secretion coupling of the insulin-producing pancreatic islet beta cell is subject to functional maturation during fetal life. We studied the maturation of a glucose-responsive insulin release from fetal rat islets and specifically investigated the impact of peptidergic regulation. To this end, islets were isolated from 21-day-old fetal rats and maintained for 7 days in tissue culture at 3.3 or 11.1 mM glucose and various supplements. In islets cultured in low glucose, acutely raising the ambient glucose concentration to 16.7 mM evoked a modest stimulation of short-term insulin release that was more pronounced in islets maintained in high glucose. Moreover, the insulin content was much higher in islets cultured in high than in low glucose. Culture with growth hormone (GH) markedly amplified both basal and stimulated short-term insulin secretion from islets maintained in either low or high glucose. Additionally, GH significantly elevated the insulin content in islets maintained in low glucose. Transforming growth factor alpha (TGF-alpha) increased basal, but not glucose-stimulated, insulin release and insulin content in islets cultured in low glucose. Gastrin, expressed in islets during fetal life, did not affect basal or glucose-stimulated insulin release, or insulin content, in islets maintained in either low or high glucose. The addition of gastrin to TGF-alpha did not affect the results obtained with the latter peptide. Gastrin-releasing peptide failed to influence basal or glucose-responsive insulin secretory rates, and insulin content, at either glucose concentration during culture. The somatostatin analog Sandostatin (octreotide acetate) neither influenced basal nor stimulated short-term insulin release at any glucose concentration present during culture, whereas the hormone significantly decreased the insulin content of islets cultured in high glucose. Pancreastatin, produced by porcine islet beta and delta cells, failed to influence basal or glucose-responsive insulin secretory rates, and islet insulin content, at either glucose concentration during culture. Culture with gastric inhibitory peptide (GIP) or glucagon-like peptide I (GLP-1), two proposed incretins, did not affect short-term insulin secretion in response to 3.3 or 16.7 mM glucose irrespective of the ambient glucose concentration during culture. To the contrary, GLP-1, but not GIP, increased the content of insulin in islets cultured in low glucose. We conclude that islet beta-cell differentiation and functional maturation of the stimulus-secretion coupling can be modulated in vitro in fetal rat pancreatic tissue by peptidergic regulation and glycemic stimulation. We suggest that GH and TGF-alpha stimulate, while somatostatin, through paracrine interaction, may inhibit, these processes. These effectors may be of regulatory significance in the in vivo development of glucose-sensitive beta cells, and defects in these mechanisms may result in glucose intolerance in adult subjects.
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PMID:Peptidergic regulation of maturation of the stimulus-secretion coupling in fetal islet beta cells. 1076 55

Neuroendocrine tumours can be visualized by several nuclear medicine modalities based on different mechanisms of cellular uptake. The most widely used radiopharmaceutical are the metaiodobenzylguanidine (123I/131I MIBG) and pentetreotide (111In pentetreotide). The first tracer follows the metabolic pathway of norephinephrine while the second one binds to somatostatin receptors which are expressed with high intensity on the neuroendocrine tissue. Some radiopharmaceuticals (Anti-CEA, Anti-CgA, Anti-GD2 monoclonal antibodies) have today only an experimental value, others such as 99mTc(V)DMSA had in the past very limited indications (medullary thyroid cancer) but at present their production is going to be stopped. An interesting series of new peptides showing a great affinity for the receptors/structures expressed by the neuroendocrine tissue is under evaluation in order to obtain a better tumour specificity. Among the positron-emitting radiopharmaceuticals, the 18F-fluorodeoxyglucose (FDG), in spite it is considered the most widely used tracer for clinical PET in oncology, did not show a satisfactory uptake in the well differentiated neuroendocrine tissues. On the contrary 18F-FDG is the best radiopharmaceutical to visualize those rare poorly differentiated neurondocrine tumours with a high proliferative index. For this reason also in this area, new radiopharmaceuticals have been studies and developed. A serotonin precursor 5-hydroxytryptophan (5-HTP) labelled with 11C has shown an increased uptake in carcinoids. Another radiopharmaceutical in development for PET is 11C L-DOPA which seems to be useful in visualizing endocrine pancreatic tumours. 18F-DOPA whole body PET may be a more promising imaging approach. Aim of this review is to summarize the potential of nuclear medicine techniques in the diagnosis of neuroendocrine tumours and to stresses the renewed role of nuclear medicine in the management of this disease.
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PMID:[Radioisotopic imaging of neuroendocrine tumours. Which radiopharmaceutical and which diagnostic procedure?]. 1178 5


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