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

Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (125I-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha 2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha 2, histamine H3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha 2, histamine H3 and somatostatin receptors to treatment of vascular headaches is suggested.
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PMID:UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms. 128 76

The authors report the case of a 48 years old man presenting a pancreatic islet cell carcinoma (gastrinoma) with liver, nodes and peritoneal metastases, associated with an elevated alpha-fetoprotein (AFP) concentration. Incomplete remission was first obtained with a chemotherapy using Streptozotocin combined with 5-Fluorouracil, in association with a Somatostatin analogue (SMS 201-995). But when relapses occur, another chemotherapy was not so effective. Serum gastrin and AFP levels had the same evolution and appear to have the same interest to follow the course of the disease.
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PMID:[Pancreatic endocrine tumor with metastases and increase of alpha-fetoprotein. A case report]. 128 58

Growth hormone and growth factors have been implicated in the pathogenesis of diabetic retinopathy. Hypophysectomy has been proposed as a treatment for proliferative diabetic retinopathy unresolved by panretinal photocoagulation (PPC). SMS 201-995, a long acting somatostatin analogue which slows down growth hormone secretion, may provide a non-invasive therapy for these rare cases. To assess this possibility, we studied the feasibility and efficiency of long-term SMS 201-995 treatment in diabetics. SMS 201-995 was injected subcutaneously with a continuous pump system at a dose of 400 micrograms/d into 4 insulin dependent diabetic patients suffering from proliferative diabetic retinopathy progressing despite a pan-photocoagulation. The mean age of these patients was 29 +/- 3 years and mean disease duration 18 +/- 3 years. Treatment periods lasted from 6 to 20 months (mean 15 months). Mean 24-hour growth hormone levels decreased by 57% after only one month of treatment (7.4 +/- 1.9 mU/l to 3.2 +/- 0.9 mU/l). The decline continued up to the third month. After the sixth month, signs of resistance to the drug were noted. The frequency of 24-hour GH peaks over 10 mU/l followed a parallel pattern. No rebound was observed when the treatment was progressively discontinued. In 2 patients neovascularization stopped. In the other 2 the process regressed. In all treatment had beneficial effects on the retina. Overall visual acuity improved (7.8 +/- 0.8/10e vs 5.5 +/- 0.8/10e). These effects were obtained within 3 to 6 months. Glycosylated haemoglobin levels did not change (8.8 +/- 1.3% to 9.0 +/- 0.8%). Insulin doses decreased 41% (46.5 +/- 1.7 U/d to 27.3 +/- 3.0 U/d). No severe hypoglycaemia occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stabilization of severe proliferative diabetic retinopathy by long-term treatment with SMS 201-995. 129

Six patients with gastrointestinal fistulae treated with a potent inhibitor of gastrointestinal hormones, the somatostatin analogue SMS 201-995 are reported. All patients had severe intraabdominal diseases and underwent a mean of 3.5 surgery procedures during their hospital stay. When the patients were analyzed individually a mean reduction of 42.5% (P < 0.050 of basal fistulae output was observed after treatment. In three patients the fistulae closed after seven and ten days of treatment with the analogue; the other three patients died after a protracted hospital stay which included multiple admissions to the Intensive Care Unit. When the output of all fistulae treated where analyzed together it showed a tendency to decrease, but it didn't reach statistical significance.
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PMID:[The somatostatin analog SMA (201-995) as adjuvant treatment in patients with external fistulae of the digestive system]. 130 33

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide originally isolated from ovine hypothalami and so called because of its ability to stimulate pituitary adenylate cyclase activity. Alternative amidation and proteolytic processing of prepro-PACAP gives rise to two bioactive-amidated forms, PACAP-NH2(1-38) (PACAP-38) and PACAP-NH2(1-27) (PACAP-27). 7B2 is a polypeptide of 185 amino acids which is predominantly found in secretory granules and is widely distributed in rat and human tissues. We investigated the ability of the two forms of PACAP to stimulate GH, prolactin and 7B2 release by the rat pituitary clonal cell line GH3, and ACTH and 7B2 by the mouse pituitary clonal cell line AtT-20. PACAP-38 and PACAP-27 stimulated 7B2 and GH/prolactin or ACTH secretion with a similar efficacy over the 2-h incubation period from GH3 and AtT-20 cells respectively. 7B2 secretion was also stimulated by corticotrophin-releasing factor (CRF-41) and vasoactive intestinal polypeptide (VIP) in AtT-20 cells, and thyrotrophin-releasing hormone (TRH) and VIP in GH3 cells. Addition of PACAP to CRF-41 resulted in an additive effect on ACTH secretion and a synergistic effect on 7B2 secretion in AtT-20 cells. No synergism was observed when PACAP was added together with TRH, either on GH and prolactin secretion or on 7B2 release from GH3 cells. PACAP-mediated 7B2 secretion from both cell lines and PACAP-stimulated ACTH release from AtT-20 cells were reduced by 5 mg octapeptide synthetic somatostatin analogue/l (5 mg SMS 201-995/l).
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PMID:Pituitary adenylate cyclase-activating polypeptide releases 7B2, adrenocorticotrophin, growth hormone and prolactin from the mouse and rat clonal pituitary cell lines AtT-20 and GH3. 131 Jul 12

This paper reports a case of pancreatic VIPoma with widespread hepatic metastasis which was treated for approximately 2 years with a synthetic somatostatin analog (SMS 201/995). The treatment of choice in cases in which the tumour was fully removable is surgical resection. This occurred rarely since approximately 80% of VIPomas are malignant and are operated late when local infiltration is already widespread; in addition, 50% of cases are already metastasised at diagnosis. In this case, due to the infiltration of the superior mesenteric artery by the primary tumour it was necessary to carry out a left pancreasectomy which included two-thirds of the neoplastic mass. This was justified by slow tumour growth and also facilitated control of diarrhea and ensured a greater efficacy of possible postoperative chemotherapy. The use of synthetic somatostatin analog (SMS 201/995) enabled diarrhea to be satisfactorily controlled and is therefore specifically indicated for this type of tumour. NSE serum assay (neuron specific enolase) allowed the evolution of disease to be monitored during follow-up.
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PMID:[VIPoma: surgical treatment]. 131 46

In the present work the effects of the novel neuropeptide Pituitary Adenylate Cyclase Activating Peptide (PACAP) on both AR4-2J cell growth and the modulation of ornithine decarboxylase activity were investigated. Both PACAP38 and the amidated form PACAP27 caused a concentration-dependent stimulation of AR4-2J cell growth; the maximal increase was seen at 1 nmol/L (30% above control, P less than 0.01) with a half-maximal effect at 0.01 nmol/L. Ornithine decarboxylase activity was also increased by PACAP in a dose-dependent manner, reaching half-maximal stimulation at 0.5 nmol/L. The addition of 1 nmol/L of somatostatin analog SMS 201-995 totally suppressed PACAP-stimulated AR4-2J cell growth. Vasoactive intestinal polypeptide (3 mumol/L) and 8-bromo-cyclic adenosine monophosphate (1 mmol/L) had no effect on cell proliferation. Treatment of cells by pertussis toxin (25 ng.mL-1.day-1) suppressed PACAP-stimulated AR4-2J cell growth but enhanced PACAP-induced stimulation of adenylate cyclase activity. It was concluded that PACAP stimulates AR4-2J cell proliferation by a mechanism that seems independent of cyclic adenosine monophosphate production. The mitogenic effect of PACAP depends on a pertussis toxin-sensitive G protein and is associated with an increase of ornithine decarboxylase activity.
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PMID:Stimulation of rat pancreatic tumoral AR4-2J cell proliferation by pituitary adenylate cyclase-activating peptide. 132 94

The somatostatin analogue octreotide (SMS 201-995) inhibits secretion and growth of certain tumor cells, and current efforts are directed toward the elucidation of its mode of antiproliferative action. In this study, the effect of octreotide on the growth of ZR-75-1 human breast cancer cells has been characterized in immunodeficient nude mice and in cell culture. These results have been related to the expression of somatostatin receptors in vivo and in vitro. Continuous infusion of 10 micrograms/kg/h of octreotide yielded plasma levels of 5.7 ng/ml and elicited highly significant growth inhibitory effects on solid ZR-75-1 breast tumors in nude mice. After 2 and 4 weeks of treatment, tumor volumes in the octreotide group were 39.1 and 36.7% of those of control animals treated with vehicle, respectively. Autoradiographic studies demonstrated that 8 of 12 ZR-75-1 tumors studied were somatostatin receptor positive. When ZR-75-1 tumor cells were exposed in vitro to nanomolar concentrations of octreotide, a dose-dependent inhibition of cell growth was observed in the presence of 5% fetal calf serum or under serum-free conditions using epidermal growth factor, insulin-like growth factor type I, or insulin as growth stimulus. In parallel receptor-binding experiments, ZR-75-1 cells were shown to express specific high-affinity somatostatin receptors (Kd value = 0.9 nM, Bmax = 6000 sites/cell). From these experiments, we conclude that octreotide is a powerful inhibitor of ZR-75-1 tumor cell growth in nude mice and in culture. This inhibitory action of octreotide and the presence of somatostatin receptors on ZR-75-1 tumor cells in vitro and in vivo suggest a direct, somatostatin receptor-mediated effect of octreotide.
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PMID:Antiproliferative effects of the somatostatin analogue octreotide (SMS 201-995) on ZR-75-1 human breast cancer cells in vivo and in vitro. 132 89

The gene encoding a novel mouse somatostatin receptor termed mSSTR3 was isolated and characterized. The sequence of mSSTR3 shows 46 and 47% identity with mSSTR1 and mSSTR2, respectively. mSSTR3 binds somatostatin-14 and somatostatin-28 with high affinity, but shows very low affinity for the somatostatin analogs MK-678 and SMS-201-995. In addition, mSSTR3 is coupled to pertussis toxin-sensitive G proteins and mediates somatostatin inhibition of forskolin-stimulated and dopamine D1 receptor-stimulated cAMP formation, indicating that it is coupled to adenylylcyclase. The pharmacological properties of mSSTR3 and its ability to couple with adenylylcyclase distinguish SSTR3 from the other cloned somatostatin receptors and indicates that it mediates biological functions different from SSTR1 or SSTR2. In situ hybridization indicates that SSTR3 mRNA is widely distributed in the mouse brain, and its expression in the nucleus of the lateral olfactory tract and in the piriform cortex, the primary olfactory cortex in the rodent brain, suggests that SSTR3 may participate in the processing and modulation of primary sensory information.
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PMID:Cloning of a novel somatostatin receptor, SSTR3, coupled to adenylylcyclase. 132 99

Many cells develop enhanced adenylate cyclase activity after prolonged exposure to drugs that acutely inhibit the enzyme and it has been suggested that this adaptation may be due to an increase in Gs alpha. We have treated wild-type and Gs alpha-deficient cyc- S49 mouse lymphoma cells with a stable analogue (SMS 201-995) of the inhibitory agonist somatostatin. After incubation with SMS for 24 h, the forskolin-stimulated cAMP synthetic rate in intact cyc- cells was increased by 76%, similar to the increase found in the wild-type cells. Forskolin-stimulated adenylate cyclase activity in the presence of Mn2+ was also increased in membranes prepared from SMS-treated cyc- cells; however, guanine nucleotide-mediated inhibition of adenylate cyclase activity was not changed despite a small decrease in inhibitory Gi alpha subunits detected by immunoblotting. Pretreatment of cyc- cells with pertussis toxin prevented SMS from inducing the enhancement of forskolin-stimulated cAMP accumulation in intact cells. After chronic incubation of cyc- cells with SMS, exposure to N-ethylmaleimide, which abolished receptor-mediated inhibition of cAMP accumulation, did not attenuate the enhanced rate of forskolin-stimulated cAMP synthesis compared to N-ethylmaleimide-treated controls. These results with cyc- cells demonstrate that an adaptive increase in adenylate cyclase activity induced by chronic treatment with an inhibitory drug can occur in the absence of expression of Gs alpha.
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PMID:Prolonged activation of inhibitory somatostatin receptors increases adenylate cyclase activity in wild-type and Gs alpha-deficient (cyc-) S49 mouse lymphoma cells. 132 4


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