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)

Previous studies have shown that somatostatin receptors on AtT-20 and GH3 pituitary tumor cells show relative preference for binding somatostatin-28 (S-28) and somatostatin-14 (S-14), respectively. Here we have attempted to determine whether this selectivity can be explained by molecular heterogeneity of the receptor. Cells were incubated with [125I-Tyr11]S-14, [125I-Leu8-D-Trp22,Tyr25]S-28, and [125I-Tyr3]SMS, and the bound ligand was chemically cross-linked with bis-[2-succinimido-oxycarbonyloxy)ethyl]sulfone, disuccinimidyl suberate, or dithiobis (succinimidyl propionate). The solubilized cross-linked material was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. [125I-Tyr11]S-14 labeled three specific receptor proteins of 57K, 42K, and 27K mol wt in AtT-20 cells. The relative proportions of the protein bands were unaltered by the use of whole cells or cell membranes or by the inclusion of dithiothreitol or antiproteolytic agents. With both [125I-Tyr11]S-14 and [125I-LTT]S-28, the 57K protein constituted the major labeled component, representing 70-75% of the total cross-linked proteins. Labeling of the three protein species by [125I-Tyr11]S-14 and [125I-LTT]S-28 was inhibited by both S-14 and S-28 in a dose-dependent manner. S-28 was 10-20 times more potent than S-14 for inhibiting the labeling by both ligands of the principal receptor species of 57K. By contrast, when a radioiodinated derivative of the octapeptide analog octreotide ([125I-Tyr3]SMS) was used as ligand, the 27K protein was preferentially labeled, whereas the 57K and 42K bands were detected only as minor components. Labeling of GH3 cells with [125I-Tyr11]S-14 and [125I-LTT]S-28 revealed three cross-linked proteins of 57K, 42K, and 27K mol wt similar to those observed in AtT-20 cells. However, in this cell line the 27K protein, not the 57K species, was the dominant component identified with these two ligands, comprising 40-50% of the total cross-linked proteins. These results suggest that there are three somatostatin receptor proteins of 57K, 42K, and 27K in pituitary cells. In AtT-20 cells, the 57K protein constitutes the major receptor protein labeled by [125I-Tyr11]S-14 and [125I-LTT]S-28, whereas the 27K protein is the major species labeled by [125I-Tyr3]SMS. The 27K, not the 57K, moiety is the principal receptor form in GH3 cells. Such ligand- and tissue-selective binding by the somatostatin receptor provides strong evidence for receptor molecular heterogeneity.
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PMID:Evidence for multiple protein constituents of the somatostatin receptor in pituitary tumor cells: affinity cross-linking and molecular characterization. 256 26

The physical properties of brain and pituitary somatostatin receptors were characterized using photocrosslinking techniques. Somatostatin receptors in rat corpus striatum and anterior pituitary membranes were covalently bound to the non-reducible somatostatin analog, [125I]CGP 23996, using the crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate and ultraviolet light. In striatal membranes, a protein of 60,000 mol. wt was labeled by [125I]CGP 23996. The binding was potently inhibited by somatostatin analogs but not by other biologically active peptides. The labeling of the 60,000 mol. wt protein by [125I]CGP 23996 was diminished by guanine triphosphate gamma thiol, which is consistent with the labeling of a somatostatin receptor coupled to guanine triphosphate binding proteins. The migration of the [125I]CGP 23996 labeled 60,000 mol. wt protein in native sodium dodecyl sulfate-gels was not affected by the reducing agent dithiothreitol, indicating that there is a general lack of disulfide bridges in the striatal somatostatin receptor. The striatal somatostatin receptor was solubilized with the detergent 3-[(3-cholamidopropyl)-dimethylaminoio]-1-propanesulfonate and specifically bound to the lectin wheat germ agglutinin, suggesting that the striatal somatostatin receptor is a glycoprotein. [125I]CGP 23996 also labeled a 60,000 mol. wt protein in anterior pituitary membranes. The characteristics of [125I]CGP 23996 binding to anterior pituitary membranes were consistent with the labeling of a somatostatin receptor. Interestingly, a comparison of the [125I]CGP 23996 labeled material from striatal and anterior pituitary membranes by two-dimensional polyacrylamide gel electrophoresis revealed the presence of several striatal somatostatin receptors of varying charge (pI values between 6 and 6.5) but only a single pituitary receptor. These findings indicate that physical differences may exist between subtypes of somatostatin receptors.
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PMID:Biochemical properties of brain somatostatin receptors. 257 Mar 75

High-performance liquid chromatography-purified 125I-vasoactive intestinal peptide (VIP) bound to T-47D human breast cancer cells in a specific, saturable, and reversible manner. Scatchard plots were compatible with the presence of one class of VIP receptors with high affinity (Kd = 4.5 X 10(-10) M VIP, and Bmax = 293 fmol/mg protein). The neuropeptide and its natural analogues inhibited the binding of 125I-VIP and stimulated cyclic AMP (cAMP) generation in T-47D cells 96-fold (EC50 = 7 X 10(-10) M VIP), in the following order of potency: VIP greater than helodermin greater than human peptide with N-terminal histidine and C-terminal methionine greater than human pancreatic growth hormone-releasing factor greater than human secretin. In contrast, 125I-VIP binding was not displaced by pancreatic glucagon, human oxyntomodulin, truncated glucagon-like peptide-1, glucagon-like peptide-2, the somatostatin analogue SMS 201-995, gastric inhibitory peptide, and a series of steroid hormones or peptides unrelated to VIP. VIP also increased cAMP generation in seven other human breast cancer cell lines: H4-66B, HSL 53, HSL 78, MCF 7, MDA-MB231, T-47D2, and ZR75-1. Adenylate cyclase activity rose from 72.2 +/- 14 to 1069 +/- 66 pmol cAMP/min mg protein after the addition of 10(-7) M VIP to T-47D plasma membranes. In agreement with our pharmacological results and the Scatchard analysis of the binding data, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized receptor in the T-47D membranes permitted identification of one autoradiographic band with a molecular weight of 69,000. The sensitivity of the Mr 69,000 binding site to GTP and low doses of VIP implies that in T-47D cells, this component constitutes the membrane domain involved in the functional regulation of adenylate cyclase by VIP receptors. Our results indicate a role for the VIP receptor-cAMP system in human breast cancer cells.
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PMID:Pharmacology, molecular identification and functional characteristics of vasoactive intestinal peptide receptors in human breast cancer cells. 284 44

In seven conscious dogs with esophagostomies and gastric cannulas, the acid, gastrin, and somatostatinlike immunoreactivity (SLI) responses to 5-min sham feeding with or without pretreatment with atropine sulfate (20 and 100 micrograms/kg) were measured. The responses to bethanechol (100 micrograms X kg-1 X h-1), to bombesin (0.5 micrograms X kg-1 X h-1) with or without pretreatment with atropine sulfate, and to a combined stimulation with bethanechol and bombesin were also measured. Sham feeding resulted in an increase in plasma SLI concentration (basal level, 20.4 +/- 4.2 pg/ml; maximally stimulated level, 46.8 +/- 5.6 pg/ml; P less than 0.01). After the injection of atropine the integrated SLI response to sham feeding was significantly decreased but not suppressed. Infusion of bethanechol did not alter SLI plasma levels. Bombesin infused alone increased the plasma SLI concentration (basal level, 15.6 +/- 2.3 pg/ml; maximally stimulated level, 55.6 +/- 10.3 pg/ml; P less than 0.01). The integrated SLI response to bombesin was significantly decreased by atropine but not significantly changed by bethanechol. These studies show that sham feeding and bombesin release somatostatin. They suggest that somatostatin release is largely under vagal-cholinergic control.
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PMID:Effects of sham feeding, bethanechol, and bombesin on somatostatin release in dogs. 285 65

The effect of electrical stimulation of the vagus nerves on the release of immunoreactive gastrin-releasing peptide (GRP), gastrin, and somatostatin was investigated using the isolated perfused rat stomach. Electrical stimulation (10 Hz, 1 ms duration, 10 V) of the peripheral end of the subdiaphragmatic vagal trunks produced a significant increase in both GRP and gastrin but a decrease in somatostatin. The infusion of atropine sulfate at a concentration of 10(-5) M augmented GRP release and reversed the decrease in somatostatin release in response to vagal stimulation to an increase above basal levels. However, the gastrin response to vagal stimulation was not affected by atropine. The infusion of hexamethonium bromide at a concentration of 10(-4) M significantly suppressed GRP release but did not affect gastrin secretion in response to vagal stimulation. On the other hand, the somatostatin response to vagal stimulation was completely abolished by hexamethonium. These findings lead us to conclude that the intramural GRP neurons might play an important role in the regulation of gastrin as well as somatostatin secretion and that somatostatin secretion may be controlled not only by a cholinergic inhibitory neuron but also by a noncholinergic, e.g., peptidergic stimulatory neuron, both of which may be regulated through preganglionic vagal fibers via nicotinic receptors. In addition, because the infusion of 10(-7) M GRP suppressed the somatostatin secretion, we suggest that either GRP should be excluded from the list of candidates for the noncholinergic stimulatory neurotransmitter for somatostatin secretion or that there are different mechanisms of action for endogenous and exogenous GRP.
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PMID:Vagal regulation of GRP, gastric somatostatin, and gastrin secretion in vitro. 285 78

Somatostatin (SRIF, SRIF-14) is a known product of the normal and malignant parafollicular cell of the thyroid. In this report we characterize SRIF production by the TT cells, a line of transformed calcitonin-producing cells derived from a human medullary thyroid carcinoma. The cells were found to contain (5-12 ng/10(6) cells) and secrete (3-10 ng/10(6) cells X 48 h) immunoreactive SRIF. Molecular sieve chromatography of cell extracts under denaturing conditions showed a major peak with a mol wt slightly larger than 12,700, probably representing pro-SRIF and a second peak which coeluted with SRIF; in one gel chromatogram a very small peak was also noted which coeluted with SRIF-28, but represented less than 0.4% of the total immunoreactive SRIF. Short term secretion of calcitonin and SRIF was stimulated by calcium in vitro (0.5-4 mM) in a dose-related manner. mRNA isolated from the TT cells hybridized to a specific bovine fetal pancreatic SRIF DNA (BFPS-2); there was no hybridization to identical amounts of mRNA from the atT-20/D16, 3T3, or RINC5F cell lines. In vitro translation of the TT cell mRNA followed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the product revealed a single protein band of approximately 13,000 daltons. It was completely abolished when the immunoprecipitation was performed in the presence of excess unlabeled SRIF. Northern transfer of TT cell cytoplasmic RNA and hybridization with FBPS-2 cDNA showed a single hybridizing band with an apparent size of approximately 750 nucleotides. Our observations demonstrate the production of SRIF by a continuous line of human medullary thyroid carcinoma cells and provide a model for studying the biosynthesis and secretion of SRIF in the parafollicular cell.
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PMID:Somatostatin production by a human medullary thyroid carcinoma cell line. 286 83

The control of release of two recently characterized forms of prolactin (PRL) of molecular mass 24 and 20 kDa was investigated. The rostral pars distalis of male tilapia was incubated singly in a hypotonic modified Krebs-Ringer bicarbonate medium in order to stimulate PRL release; for comparison, the proximal pars distalis containing growth hormone (GH) cells was incubated in isotonic medium with or without 1 microgram/ml cortisol to stimulate GH release. The release of both PRLs and GH into the medium was measured by sodium dodecyl sulfate (SDS)--polyacrylamide gel electrophoresis followed by densitometry. Both somatostatin and synthetic (Gillichthys) urotensin II, a partial somatostatin homolog and analog from the teleost caudal neurosecretory system, significantly inhibited the release of both PRLs. Somatostatin significantly inhibited GH release, but urotensin II had no significant effect.
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PMID:In vitro effects of somatostatin and urotensin II on prolactin and growth hormone secretion in tilapia, Oreochromis mossambicus. 287 18

The receptor for somatostatin present in rat pancreatic plasma membranes was characterized by affinity labeling with [125I-Tyr11]somatostatin utilizing three different heterobifunctional cross-linking agents: N-5-azido-2-nitrobenzoyloxy-succinimide, N-succinimidyl 6-(4-azido 2'-nitrophenylamine)hexanoate, and N-hydroxysuccinimidyl 4-azido-benzoate. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed a broad band of Mr = 92,000 when any of the three cross-linkers was used; N-succinimidyl 6-(4-azido 2'-nitrophenylamine), however, was most efficient. Labeling of the Mr = 92,000 protein band was not affected by reducing agents but was sensitive to somatostatin and guanine nucleotides, particularly GTP gamma S, at concentrations which reduced binding to the receptor. The affinity-labeled protein could be solubilized completely with Zwittergent 3-12, partially with Triton X-100 and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid, and poorly with Zwittergent 3-08 and digitonin. When exposed to agarose-coupled lectins, the detergent solubilized, labeled Mr = 92,000 protein was completely adsorbed to wheat germ agglutinin, partially to ricin communis II, and not at all to concanavalin A or lotus or lentil lectin. The Mr = 92,000 protein bound to wheat germ agglutinin-agarose was not eluted by N-acetylglucosamine but was by triacetylchitotriose, providing a considerable purification of the somatostatin receptor. These data allow us to conclude that the somatostatin receptor is a monomeric glycoprotein with an Mr = 90,000 binding subunit which probably contains a polymeric arrangement of N-acetylglucosamine residues.
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PMID:Characterization of covalently cross-linked pancreatic somatostatin receptors. 287 90

This work was undertaken to study the effect of glucose on pancreaticoduodenal and peripheral venous somatostatin-like immunoreactivity (SLI) levels in dogs. Our experiments were performed in normal and alloxan diabetic dogs, conscious or anesthetized. The response of somatostatin was studied following intravenous (0.2 g/kg) or oral (1 g/kg) glucose administration. SLI levels were assayed in peripheral venous blood and in superior pancreaticoduodenal venous blood. An interplay of the cholinergic nervous system was challenged both after oral and intravenous glucose load by a prior administration of atropine sulfate (0.2 mg/kg i.v.). Our results show that (a) peripheral venous SLI levels do not reflect pancreatic D-cell activity in alloxan diabetic as in normal animals. (b) Increase of peripheral venous SLI level after oral glucose is under cholinergic nervous system control. (c) In alloxan diabetic dogs, the response of pancreaticoduodenal venous SLI to intravenous glucose was decreased, whereas peripheral SLI response to oral glucose was increased.
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PMID:In vivo study of glucose-induced somatostatin secretion: comparison in normal and alloxan-diabetic dogs. 289 26

The functional and biochemical characteristics of somatostatin (somatotropin release-inhibiting factor) (SRIF) receptor subtypes were examined in the clonal pituitary cell lines AtT-20 and GH3. SRIF inhibits evoked calcium influx into each of these cell lines. The rank order of potencies of structural analogues of SRIF to inhibit calcium influx into GH3 versus AtT-20 cells was different. Inhibitory actions of SRIF on calcium influx desensitized in AtT-20 cells but not GH3 cells. The biochemical properties of the SRIF receptor subtypes in AtT-20 and GH3 cells were assessed by photoaffinity labeling of each receptor with the nonreducible SRIF analogue [125I]CGP 23996 and the photocrosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. The covalently labeled receptors in both cell lines had the same size, 55 +/- 5 kDa, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The covalent binding of [125I]CGP-23996 to GH3 and AtT-20 cell membranes was blocked by 1 microM SRIF, somatostatin 28, Trp8-SRIF and was GTP sensitive. Analysis of the labeled receptors in GH3 and AtT-20 cell membranes by two-dimensional polyacrylamide gel electrophoresis indicated that they were of similar charge (pI = 6-6.5) and that they comigrate when applied together. Proteolysis of the GH3 and AtT-20 cell SRIF receptors with Staphylococcus aureus V-8 and thermolysin revealed similar peptide maps. Pretreatment of AtT-20 cells with different stable SRIF analogues abolished the subsequent equilibrium or covalent labeling of the SRIF receptor with [125I]CGP-23996. Similar treatment of GH3 cells did not reduce the covalent labeling of the SRIF receptor by [125I]CGP 23996. These studies indicate that the functional characteristics of SRIF receptors in GH3 and AtT-20 cells are different. However, clear differences in the biochemical properties of these receptor subtypes were not observed. Subtle variations in the structure of the SRIF receptors may therefore be responsible for the functional differences.
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PMID:Somatostatin receptor subtypes in the clonal anterior pituitary cell lines AtT-20 and GH3. 289 89


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