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)

Dynorphin A(1-17), the proposed endogenous ligand for the kappa receptor, has been reported to demonstrate no antinociceptive activity when tested in analgesic assays involving noxious (heat (e.g., tail-flick and hot-plate assays). By using a rat tail-flick analgesic assay that utilizes extreme cold as its noxious stimulus (an ethylene glycol-water mixture maintained at -10 degrees C), we have recently reported a dose-related and naloxone-reversible antinociceptive effect for i.c.v. administered dynorphin A(1-17). To elucidate the biochemical mechanism of this antinociception, we designed a push-pull perfusion system which would allow us to measure changes in neuropeptide release in the spinal cord during exposure to noxious heat or cold. Male Sprague-Dawley rats were implanted surgically with two lengths of PE-10 tubing inserted into the spinal subarachnoid space via the cisterna magna, with the push cannula at the level of T-1, and the pull cannula at the rostral edge of the lumbar enlargement. At the time of testing, samples of cerebrospinal fluid were collected both in the presence and absence of a noxious stimulus. Substance P (SP) and somatostatin (SST) levels were measured by radioimmunoassay. Exposing the animal's tail to the noxious cold (30 sec/min for 20 min) resulted in a significant elevation in SP release (69% above base-line levels), but no change in the level of SST release. Conversely, exposure to noxious heat (50 degrees C, 20 sec/min for 20 min) produced a significant increase in SST release (56% above base line), but no change in the level of SP release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential release of substance P and somatostatin in the rat spinal cord in response to noxious cold and heat; effect of dynorphin A(1-17). 169 Feb 93

Cells prepared from frog esophageal peptic glands by dispersal in low-Ca2+ medium (peptic acini) or 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-containing medium ("EGTA cells") were compared. EGTA cells were characterized by decreased secretory responses to agonists [bombesin (BB), acetylcholine, and isoproterenol] and intracellular messenger activators (forskolin, 12-O-tetradecanoyl-phorbol-13-acetate), decreased relative intrinsic efficacies of muscarinic agonists, and somatostatin insensitivity. Decreased BB and muscarinic receptor responses were not associated with changes in receptor number or characteristics. The time course of BB- and acetylcholine-stimulated pepsinogen secretion indicated that the marked reduction was confined largely to the late secretory phase (2-30 min), dependent on extracellular Ca2+, rather than early phase (less than 2 min) secretion, which is related to release of intracellular Ca2+. The defect could be reversed by the Ca2+ ionophore A23187. BB-stimulated intracellular Ca2+ mobilization measured with fura-2/AM was similar in the two cell preparations, whereas BB-stimulated 45Ca2+ uptake was reduced threefold in EGTA cells, and this defect was also reversed by A23187. Somatostatin inhibited both BB-stimulated secretion and 45Ca uptake by peptic acini, but it had no significant effect on these parameters in EGTA cells. Cytochalasin B inhibited BB stimulation in peptic acini but not EGTA cells. These findings suggest that peptic cells isolated with EGTA exhibit decreased secretory responses that are due at least in part to impairment of a mechanism for uptake of extracellular Ca2+.
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PMID:Decreased secretion due to a Ca2+ influx defect in frog peptic cells isolated with EGTA. 215 19

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

The present study was undertaken to investigate how a somatostatin analog (201-995 Sandoz), which is now commonly used for treatment of patients with gut hormone-producing tumors, affects water and ion absorption and transit time in the normal jejunum. Six healthy volunteers were given somatostatin analog intravenously at a dose of 1 microgram/kg/hr. At the same time, jejunal water and ion movement and transit time were measured using the triple-lumen tube technique [perfusion of a plasma-like electrolyte solution with PEG as a nonabsorbable marker at a rate of 15 ml/min; dye dilution curves ([3H]mannitol, [14C]PEG, BSP) for determination of jejunal transit time]. During somatostatin analog administration, transit time through a 30-cm segment of perfused jejunum increased from 4.0 min to 17.0 min. While the somatostatin analog increased jejunal transit time, it had no effect on net water and electrolyte absorption under steady-state conditions. The effect of somatostatin analog on the proximal small bowel is similar to the action of an eight-times higher dose of intravenous native somatostatin previously studied. The effect of the analog on transit time suggests a potentially beneficial effect in patients with large-volume diarrhea in which no tumor or circulating secretagogue can be identified, such as in pseudopancreatic cholera syndrome.
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PMID:Effect of somatostatin analog on water and electrolyte transport and transit time in human small bowel. 288 8

A fraction increasing water and sodium absorption in rat duodenum was detected in the material obtained at an early stage of purification of the hitherto isolated duodenal hormones. In Wistar rats, duodenal loops were made in situ and filled with a solution containing 0.138 mM NaCl, with 14C PEG and 22Na as markers; the final content was collected after 1 h and the movements of water and Na measured. In contrast to secretin, cholecystokinin, and somatostatin, which induced duodenal secretion, and with pentagastrin, which induced duodenal absorption and stimulated acid secretion, this fraction induced duodenal absorption f Na and water without stimulating acid secretion. The fraction was obtained by chromatography of a concentrate of intestinal peptides in 0.2 M acetic acid on Sephadex G25 (fine), and its active component was found to be methanol-soluble at pH4 and insoluble at pH7.5. It was eluted from carboxymethylcellulose 22 with 0.04 M ammonium bicarbonate and gel filtration of Sephadex G50 *fine), resulting in a tenfold increase in activity. Incubation with chymotrypsin suppressed the biological activity, indicating a peptidic nature. The substance displayed biological and radioimmunological properties distinct from those of the gastrointestinal hormones. Particularly, no cross-reactivity was found with gastrin, prolactin, and angiotensin, which are known to increase intestinal absorption. It therefore seems possible that the activity described is due to a peptide that has as yet not been isolated. The name 'sorbin' is proposed for this active principle.
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PMID:Sorbin, a peptide contained in porcine upper small intestine which induces the absorption of water and sodium in the rat duodenum. 679 42

The influence of low temperature and high viscosity on the conformation of somatostatin and two of its analogues was investigated by 1H NMR in solution. The conformation of native somatostatin, a cyclic octapeptide agonist DC13-116 and a linear octapeptide agonist were compared in ethylene glycol at 303 K and in methanol at low temperature. The first goal of this study was to investigate if either low temperature or high viscosity is the more important for the reduction of the conformational freedom. Secondly we wanted to compare the amount of information concerning the conformation present in both solvents. A larger amount of NOESY cross-peaks is observed in ethylene glycol at room temperature compared to methanol at low temperature. This indicates that the raising of the viscosity is a more important factor in reducing the flexibility of peptides than the lowering of the temperature.
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PMID:Comparing conformations at low temperature and at high viscosity. Conformational study of somatostatin and two of its analogues in methanol and in ethylene glycol. 772 99

Increased choleresis of up to 4950 ml per day was observed after positioning of a PTCD in a patient with complete biliary obstruction due to a malignant tumor. Bile secretion could be temporarily reduced to 15% of the initial flow rate by intravenous administration of somatostatin. Simultaneously, the concentration of bile acids increased from 1.2 to 6.2 mmol/l, whereas the concentrations of electrolytes remained constant. Cholic acid had no influence on bile secretion. To safeguard the patient from excessive loss of fluid and electrolytes, the drained bile was reinfused into the duodenum via a PEG.
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PMID:[Post-cholestatic hypercholeresis in a patient with malignant obstruction of the bile ducts]. 834 4

The glycopeptide hormone catfish somatostatin (somatostatin-22) has the amino acid sequence H-Asp-Asn-Thr-Val-Thr-Ser-Lys-Pro-Leu-Asn-Cys-Met-Asn-Tyr-Phe-Trp-Lys-Se r-Arg-Thr-Ala-Cys-OH; it includes a cyclic disulfide connecting the two Cys residues, and the major naturally occurring glycoform contains D-GalNAc and D-Gal O-glycosidically linked to Thr5. The linear sequence was assembled smoothly starting with an Fmoc-Cys(Trt)-PAC-PEG-PS support, using stepwise Fmoc solid-phase chemistry. In addition to the nonglycosylated peptide, two glycosylated forms of somatostatin-22 were accessed by incorporating as building blocks, respectively, Nalpha-Fmoc-Thr(Ac3-alpha-D-GalNAc)-OH and Nalpha-Fmoc-Thr(Ac4-beta-D-Gal-(1-->3)-Ac2-alpha-D-GalNAc)-O H. Acidolytic deprotection/cleavage of these peptidyl-resins with trifluoroacetic acid/scavenger cocktails gave the corresponding acetyl-protected glycopeptides with free sulfhydryl functions. Deacetylation, by methanolysis in the presence of catalytic sodium methoxide, was followed by mild oxidation at pH 7, mediated by Nalpha-dithiasuccinoyl (Dts)-glycine, to provide the desired monomeric cyclic disulfides. The purified peptides were tested for binding affinities to a panel of cloned human somatostatin receptor subtypes; in several cases, presence of the disaccharide moiety resulted in 2-fold tighter binding.
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PMID:Chemical synthesis and receptor binding of catfish somatostatin: a disulfide-bridged beta-D-Galp-(1-->3)-alpha-D-GalpNAc O-glycopeptide. 1066 64

Recently, the medical approach to patients with secreting and clinically non-functioning pituitary adenomas has received great impulse thanks to the availability of new, selective and long-lasting compounds with dopaminergic activity, such as cabergoline, and of somatostatin analogues provided in slow-release formulations, such as lanreotide and octreotide long acting release (LAR). In particular, the use of cabergoline has induced control of hyperprolactinaemia and tumour shrinkage in the great majority of patients with micro- and macroprolactinomas. Cabergoline treatment restores fertility both in women and men, and partially improves osteoporosis, one of the major complications of hyperprolactinaemia. In acromegaly, disease control (growth hormone [GH] <2.5-1.0 microg/l as a fasting or glucose-suppressed value, respectively, together with age-normalised insulin-like growth factor [IGF]-I) is achievable in more than half of patients receiving treatment with lanreotide or octreotide-LAR. Improvement in cardiomyopathy, sleep apnoea and arthropathy has been reported during GH/IGF-I suppression after pharmacotherapy. A synthetic GH analogue, B2036-PEG, that antagonises endogenous GH binding to its receptor-binding sites and a GH-releasing hormone antagonist that blocks the effect of this releasing factor on the hypothalamus and pituitary are presently under investigation in acromegaly. Preliminary studies have clearly demonstrated the effectiveness of the GH receptor antagonist in suppressing IGF-I levels in acromegalic patients previously unresponsive to somatostatin analogues. Beneficial effects of subcutaneous octreotide and lanreotide have also been reported in adenomas secreting thyroid-stimulating hormone, while the results of treatment with dopamine agonists or somatostatin analogues remain disappointing in patients with clinically non-functioning adenomas. In these patients the possibility of visualising in vivo the expression of D(2) receptors using specific radiotracers such as (123)I-methoxybenzamide has allowed selection of patients likely to respond to cabergoline. Scant effects of pharmacotherapy have also been reported in patients with adenomas secreting adrenocorticotropic hormone. However, some preliminary data suggest a potential use of cabergoline in combination with ketoconazole, or alone, in selected cases of Cushing's disease or Nelson's syndrome.
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PMID:New medical approaches in pituitary adenomas. 1097 Nov 10

The available somatostatin analogs for subcutaneous administration lower growth hormone (GH) levels in more than 90% of patients and Insulin-like growth factor-I (IGF-I) levels in up to 60%. They are also capable of reducing tumor size in up to 50%. Recently long-acting somatostatin analogs were introduced. The use of these application forms can result in normalization of IGF-1 in 60% of patients after 1 year and in 75% after 3 years. The development of selective analogs for the somatostatin receptor subtype-5 potentially will enhance the potency and the spectrum of the medical treatment of acromegaly with somatostatin analogs. The new generation of dopaminergic drugs also form a potentially effective and well tolerated therapy that should be considered in the management of those acromegalic patients, which have relative low serum IGF-I concentrations, along with high serum prolactine levels. Finally, growth hormone receptor (GHR) antagonists are under development for the use in humans. Preliminary results look promising, when biochemical parameters are concerned. Interim analysis of a phase 3 study with B2036-PEG in 38 patients does show that normalization of IGF-I concentrations is reached in at least 92% of the treated patients.
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PMID:New medical treatment for acromegaly. 1108 Nov 77


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