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)

We studied the functional coupling between antral somatostatin and gastrin cells in pigs using isolated perfused preparations of the antrum with intact supply of the vagus nerves. Luminal acidification significantly inhibited gastrin secretion to 61 +/- 3% of basal secretion and increased somatostatin output 9-fold. Intra-arterial infusion of somatostatin to concentrations of 10(-10) and 10(-9) mol/l inhibited gastrin secretion to 18 +/- 9 and 33 +/- 11% of basal secretion. Electrical stimulation of the vagus nerves and intra-arterial infusion of gastrin-releasing polypeptide (GRP; 10(-9) mol/l) significantly increased both gastrin and somatostatin secretion. Addition to the perfusate of Fab fragments of somatostatin antibodies abolished the effect of somatostatin at 10(-10) mol/l and the acid inhibition of gastrin secretion, but had no effect on the response to vagus stimulation of GRP infusion. We conclude that a local release of somatostatin is essential for the acid-induced inhibition of gastrin secretion, whereas changes in the local somatostatin concentration are unlikely to play a major role in vagally or GRP-induced gastrin secretion.
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PMID:Somatostatin is an essential paracrine link in acid inhibition of gastrin secretion. 135 90

The methods for treatment of advanced prostate cancer, based on the agonistic analogs of LH-RH were reviewed. New therapeutic approaches utilizing antagonistic analogs of LH-RH such as SB-75 (Cetrorelix) have been described. Analogs of LH-RH chemically linked to various cytotoxic radicals are also being developed. Combinations of LH-RH agonists or antagonists with superactive somatostatin analogues such as Octastatin (RC-160) or with bombesin/GRP antagonists are being investigated in order to delay or prevent the relapse and improve the therapy for prostate cancer.
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PMID:Present status of agonistic and antagonistic analogs of LH-RH in the treatment of advanced prostate cancer. 136 77

Physiological stimuli from inside and outside the stomach coverage on gastric effector neurons that are the primary regulators of acid secretion. The effector neurons comprise cholinergic neurons and two types of non-cholinergic neurons: bombesin/GRP and VIP neurons. The neurons act directly on target cells or indirectly by regulating release of the hormone, gastrin, the stimulatory paracrine amine, histamine, and the inhibitory paracrine peptide, somatostatin. In the antrum, cholinergic and bombesin/GRP neurons activated by intraluminal proteins stimulate gastrin secretion directly and, in the case of cholinergic neurons, indirectly by eliminating the inhibitory influence of somatostatin (disinhibition). In turn, gastrin acts on adjacent somatostatin cells to restore the secretion of somatostatin. The dual paracrine circuit activated by antral neurons determines the magnitude of gastrin secretion. Low-level distention of the antrum activates, preferentially, VIP neurons that stimulate somatostatin secretion and thus inhibit gastrin secretion. Higher levels of distention activate predominantly cholinergic neurons that suppress antral somatostatin secretion and thus stimulate gastrin secretion. In the fundus, cholinergic neurons activated by distention or proteins stimulate acid secretion directly and indirectly by eliminating the inhibitory influence of somatostatin. The same stimuli activate bombesin/GRP and VIP neurons that stimulate somatostatin secretion and thus attenuate acid secretion. In addition, gastrin and fundic somatostatin influence acid secretion directly and indirectly by regulating histamine release. Acid in the lumen stimulates somatostatin secretion, which attenuates acid secretion in the fundus and gastrin secretion in the antrum.
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PMID:Neural, hormonal, and paracrine regulation of gastrin and acid secretion. 136 24

This work investigates the effects of the long-acting somatostatin analogue, octreotide also named SMS 201-995 or Sandostatin, on pancreatic growth in function of the dose and duration of treatment. Octreotide was administered s.c. twice daily, while pancreatico-trophic peptides, caerulein and CCK-8 (1.8 nmol/kg b.wt.) or GRP (3.6 nmol/kg b.wt.) were administered s.c. three times daily. Octreotide (1,10,20 micrograms/kg b.wt.) administered for 4 days reduced pancreatic growth induced by caerulein in a dose-dependent manner. This effect, significant from 10 micrograms/kg, was more obvious with 20 micrograms/kg. At this latter dose, octreotide inhibited significantly the increase in pancreatic weight and protein, RNA, DNA and enzyme content induced by a 4- or 10-day treatment with GRP. A similar effect was observed after a 4-day treatment with CCK-8, but after a 10-day treatment only protein and enzyme contents were reduced. Octreotide by itself did not affect pancreatic size and composition after a 10-day treatment, but decreased enzyme content after a 4-day treatment. It is concluded that octreotide exerts an antitrophic effect on the rat exocrine pancreas which depends on the dose and duration of treatment and can be modulated by the trophic factor applied for a long-term.
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PMID:Effect of prolonged administration of long-acting somatostatin on caerulein, CCK-8 and GRP induced pancreatic growth in the rat. 170 49

We have found vasoactive intestinal polypeptide (VIP)-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide (CGRP-2)-, and somatostatin-like immunoreactivities in extracts of sporadic human parathyroid adenomas (n = 18). The content of CGRP-2, substance P, and somatostatin in adenomas correlated directly with that of parathyroid hormone. In addition, concentrations of VIP versus substance P and somatostatin versus CGRP-2 in adenomas were directly correlated. Neuropeptide content of parathyroid hyperplasias differed from that of adenomas. VIP was detected in only one of seven parathyroid hyperplasias, and neurotensin was undetectable (0/7), whereas substance P was present in six of seven cases and GRP in five of seven hyperplasias. In hyperplasias, content of substance P correlated directly with that of gastrin-releasing peptide. Peroxidase immunohistochemistry localized VIP-like immunoreactivity to 20% to 50% of both chief and oxyphilic cells and rare clear cells and capillary endothelium in 11 of 12 adenomas studied. Focal staining was present in glandular epithelium of the rim of adjacent normal parathyroid tissue and in two of three normal parathyroid glands removed with thyroid goiters. This staining was both cytoplasmic and apical membrane. By contrast, in adenomas, neurotensin- and substance P-like positivities were confined to scattered (5% to 10%) oxyphilic cells. Cytoplasmic positivity for parathyroid hormone, noted in 30% to 70% of cells in serial sections, confirmed that these tissues were indeed parathyroid glands.
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PMID:Vasoactive intestinal polypeptide-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide-, and somatostatin-like immunoreactivities in human parathyroid glands. 172 Sep 2

The influence of intragastric pH on the basal release of somatostatin has been studied in healthy controls and in duodenal ulcer patients. In addition the somatostatin response to gastrin-releasing peptide infusion has been evaluated both regarding the effect of intragastric pH and the influence of vagal innervation and muscarinic blockade. No difference was found in basal blood levels, when changing the intraluminal pH, although a slightly higher basal somatostatin concentration was noticed in patients with duodenal ulcer disease. Neither proximal gastric vagotomy nor cholinergic blockade had any effect on basal somatostatin concentrations. GRP infused in stepwise increasing doses from 20 pmol/kg/h to 400 pmol/kg/h induced a small but significant response. This effect of GRP was most evident, when the stomach was perfused with 0.1 M HCl. The small, somatostatin response to GRP infusion was not influenced by vagal denervation of the parietal cell area, neither by cholinergic blockade. Despite the previously observed effects of vagotomy and cholinergic blockade on gastrin release induced by GRP, a corresponding inverse effect on somatostatin is not apparent.
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PMID:Somatostatin release induced by gastrin-releasing peptide in man. Effect of proximal gastric vagotomy and cholinergic blockade. 197 87

The binding of 125I-Tyr4 bombesin was investigated on plasma membranes of 8 human breast cancer cell lines and 2 long-term cultures of normal human breast epithelial cells. Scatchard plots were compatible with high-affinity, single-site class of receptors in 3 cell lines (KD of 0.75 x 10(-9) and 10(-9) M, Bmax of 0.75 x 10(-13) and 9.7 x 10(-13) M/mg protein in MDA-MB231 and in T47D cells, respectively) while no binding was observed in 5 other cell lines and normal epithelial cells. The neuropeptide and its structural analogues (natural or synthetic) inhibited the binding of 125I-Tyr4 bombesin in the following order of potency: gastrin-releasing peptide (GRP, EC50 = 1.7 x 10(-10) M) greater than BIM 26159 greater than bombesin, Tyr4 bombesin greater than BIM 26147 greater than litorin greater than neuromedin C. In contrast, 125I-Tyr4 bombesin binding was not displaced by neuromedin B, somatostatin, bradykinin and insulin. In agreement with our binding data, SDS-PAGE of the complex 125I-Tyr4 bombesin-receptor covalently linked by ethylene glycol-bis succinimidyl succinate (EGS) identified after autoradiography a single band with a molecular weight of 75,000, which disappeared in the presence of bombesin in excess. No transcription of either GRP or neuromedin B mRNA could be shown in tumor or normal cells. Exogenous gastrin-releasing peptide had no effect on growth of the cell lines when a serum-free medium was used, implicating that in breast cancer cell lines this receptor does not mediate growth but has a functional role.
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PMID:Characterization, in some human breast cancer cell lines, of gastrin-releasing peptide-like receptors which are absent in normal breast epithelial cells. 216 13

Adult onset nesidioblastosis (AON) is an extremely rare entity associated with hypersecretion of insulin. Previous reports have demonstrated that the somatostatin analog, Sandostatin (SMS), will control the clinical symptoms induced by infantile nesidioblastosis. We hypothesized that insulin, C-peptide, and secondary peptide secretion from AON is provocable. We also hypothesized that SMS would suppress both basal and provoked primary and secondary peptide secretion in AON. To test this hypothesis, in a patient with AON, 13 gut peptide levels were determined at set intervals during provocative testing with a test meal, a calcium infusion, a secretin bolus, and a glucagon bolus. These tests were repeated under the influence of SMS. Insulin, C-peptide, and pancreatic polypeptide (PP) levels were elevated in the basal state. SMS suppressed all three peptides (mean 68%) (p less than 0.05). Basal fasting glucose rose by 65%, and glucose ratios were raised throughout all four tests. Insulin:glucose ratios decreased during SMS therapy. Insulin and PP secretion was increased by all four provocative tests (mean 458% and 665% above baseline, respectively). C-peptide was provoked by three tests (mean 204%). Peptides with normal basal values were also provocable. GRP and glucagon were provoked by secretin stimulation (182%, 186%, respectively). Calcium infusion stimulated CIP release by 372%. SMS suppressed the peak provoked peptide levels in all positive provocation tests (p less than 0.05). Peak provoked insulin values were decreased by 59%, C-peptide by 75%, and PP by 92%. Peak provoked glucagon, CRP, neurotensin, and GIP levels were decreased by 20%, 65%, 51%, and 73%, respectively. The patient has been maintained on SMS (25 micrograms bid) for 1 yr and has shown decreased insulin levels, normal glucose levels, and, at 1 yr, leads an asymptomatic normal life. SMS is able to suppress primary and secondary peptide secretion in both the fasting and provoked state. The long-term efficacy of SMS may be predicted by its ability to suppress primary peptide release during peak provocation.
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PMID:Adult onset nesidioblastosis: response of glucose, insulin, and secondary peptides to therapy with Sandostatin. 240 44

At present our knowledge of enteric peptide-containing neurons in man is limited. In this study we have used human appendices removed at surgery to examine the peptidergic innervation by immunocytochemistry, immunochemistry, and pharmacological in vitro experiments. Immunocytochemistry revealed a variety of peptide-containing nerve fiber populations in the human appendix. VIP/PHI-, VIP/PHI/NPY-, SP/NKA-, galanin-, and enkephalin-containing nerve fibers were numerous; CGRP- and GRP-containing nerve fibers were moderate in number, while only scattered NPY-, enkephalin/BAM-, and somatostatin-containing nerve fibers could be found. No CCK-, dynorphin A-, or dynorphin B-immunoreactive nerve fibers could be detected. The coexistence of VIP/PHI, SP/NKA, and enkaphalin/BAM can be anticipated from the known sequence of their respective precursors. However, the coexistence of VIP/PHI and NPY was unexpected but corroborates previous observations in other species. Interestingly, SP and CGRP did not seem to coexist in nerve fibers of the human appendix. Immunochemistry (RIA and HPLC) confirmed the presence of VIP, NPY, SP, galanin, CGRP, GRP, enkephalin, and somatostatin. Motor activity studies suggest that acetylcholine plays a major role in the electrically evoked contractions, since atropine suppressed these contractions. Galanin (10(-8)-10(-6) M) and GRP (10(-9)-10(-7) M) caused concentration-dependent contractions that were unaffected by tetrodotoxin and thus probably reflect a direct action on smooth muscle receptors. GRP (10(-9) M) enhanced the electrically induced cholinergic contraction (to 193 +/- 24%), while met-enkephalin (10(-6) M) reduced it (to 54 +/- 6%). Both peptides failed to affect the contractile response to exogenous acetylcholine and probably act to modulate the release of acetylcholine. NPY, VIP, CGRP, SP, and somatostatin failed to induce contraction or to affect the electrically evoked contractions.
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PMID:Neuropeptides in the human appendix. Distribution and motor effects. 247 67

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87


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