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)

The influence of somatostatin was studied on cyclic AMP levels and adenylate cyclase activity in cyc- variants of S49 lymphoma cells. These cells are deficient in the guanine nucleotide site that mediates hormone-induced adenylate cyclase stimulation, but their cyclase can be stimulated by forskolin. Somatostatin maximally decreased the 30 microM forskolin-stimulated cyclic AMP levels by 35%. Half-maximal suppression occurred at about 0.1 nM somatostatin. Somatostatin (up to 1 microM) had no effect on the 100 microM forskolin-stimulated adenylate cyclase activity in cyc- membrane preparations when guanine nucleotides were not present. In the presence of GTP, however, which by itself caused a small decrease in activity, somatostatin maximally inhibited the enzyme by 20-25%. GTP was half-maximally effective at 0.1 microM, and half-maximal inhibition by somatostatin was observed at 0.1- 1 nM. In the presence of the stable GTP analog guanosine 5'-O-(3-thiotriphosphate) (1 microM), which decreased the stimulated activity by about 40% after a short lag period, somatostatin (1 microM) did not cause a further decrease in final activity but reduced the lag period by about 50%. The data indicate that membranes of cyc- variants contain a regulatory site that mediates both guanine nucleotide and hormone-induced inhibition of the adenylate cyclase and suggest that the mechanisms of activation and inactivation of this inhibitory site are similar to those of the stimulatory component missing in cyc-membranes.
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PMID:Occurrence of a hormone-sensitive inhibitory coupling component of the adenylate cyclase in S49 lymphoma cyc- variants. 613 5

The influence of somatostatin was studied on GTPase activity in membranes of cyc- and H21a variants of S49 lymphoma cells, which are functionally defective in the guanine nucleotide site (Ns) mediating hormonal stimulation of the adenylate cyclase. Somatostatin, which inhibits adenylate cyclase in these membranes by a GTP-dependent process, caused a concomitant activation of a high-affinity GTPase (apparent Km approximately equal to 0.2 microM) by 40-50%. The hormone-stimulated GTPase also exhibited an apparent Km value of about 0.2 microM. GTPase stimulation by somatostatin occurred without an apparent lag phase. There was a close correlation between adenylate cyclase inhibition and high-affinity GTPase stimulation induced by somatostatin. Various other peptide hormones studied and isoproterenol had no effect on GTP hydrolysis. Activation of the enzyme by somatostatin was reduced or abolished by pretreatment of the membranes with the SH reagent, N-ethylmaleimide. In membranes of wild-type S49 lymphoma cells, somatostatin caused an increase in GTPase activity similar to that in cyc- and H21a membranes. The data show that cyc- and H21a membranes, which are more or less defective in Ns, contain a hormone-sensitive, high-affinity GTPase and that the activation of this enzyme is closely related to adenylate cyclase inhibition by somatostatin. The data suggest that, similar to Ns, the activity state of the guanine nucleotide site (Ni), which apparently mediates somatostatin-induced inhibition of the adenylate cyclase, is controlled by a high-affinity GTPase.
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PMID:Somatostatin-induced stimulation of a high-affinity GTPase in membranes of S49 lymphoma cyc- and H21a variants. 613 2

The inhibitory and stimulatory guanine nucleotide-binding regulatory components (Gi and Gs) of adenylate cyclase both have an alpha X beta subunit structure, and the beta subunits are functionally indistinguishable. GTP-dependent hormonal inhibition of adenylate cyclase and that caused by guanine nucleotide analogs seem to result from dissociation of the subunits of Gi. Such inhibition can be explained by reduction of the concentration of the free alpha subunit of Gs as a result of its interaction with the beta subunit of Gi in normal Gs-containing membranes. However, inhibition in S49 lymphoma cyc- cell membranes presumably cannot be explained by the Gi-Gs interaction, since the activity of the alpha subunit of Gs is not detectable in this variant. Several characteristics of Gi-mediated inhibition of adenylate cyclase have been studied in both S49 cyc- and wild type membranes. There are several similarities between inhibition of forskolin-stimulated adenylate cyclase by guanine nucleotides and somatostatin in cyc- and wild type membranes. 1) Somatostatin-induced inhibition of the enzyme is dependent on GTP; nonhydrolyzable GTP analogs are also effective inhibitors. 2) The effect of guanosine-5'-(3-O-thio)triphosphate (GTP gamma S) is essentially irreversible, and somatostatin accelerates GTP gamma S-induced inhibition. 3) Inhibition of adenylate cyclase by somatostatin or Gpp(NH)p is attenuated by treatment of cells with islet-activating protein (IAP). 4) Both cyc- and wild type membranes contain the substrate for IAP-catalyzed ADP-ribosylation (the alpha subunit of Gi). 5) beta Subunit activity in detergent extracts of membranes is liberated by exposure of the membranes to GTP gamma S. The alpha subunit of Gi in such extracts has a reduced ability to be ADP-ribosylated by IAP, which implies that this subunit is in the GTP gamma S-bound form. The resolved subunits of Gi have been tested as regulators of cyc- and wild type adenylate cyclase under a variety of conditions. The alpha subunit of Gi inhibits forskolin-stimulated adenylate cyclase activity in cyc-, while the beta subunit stimulates; these actions are opposite to those seen with wild type membranes. The inhibitory effects of GTP plus somatostatin (or GTP gamma S) and the alpha subunit of Gi are not additive in cyc- membranes. In wild type, the inhibitory effects of the hormone and GTP gamma S are not additive with those of the beta subunit.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Subunit dissociation and the inhibition of adenylate cyclase in S49 lymphoma cyc- and wild type membranes. 614 91

Apart from the very frequent HIV encephalitis, which lays the foundation for opportunistic infections, the most common diseases encountered in HIV-infected patients are toxoplasmosis and lymphoma; the percentage of cases of other diseases is very small. It is capital to diagnose cerebral lymphoma at an early stage in these patients who already are in a precarious general and neurological state since this type of lesion usually occurs late in the natural course of AIDS. In the differential diagnosis between toxoplasmosis and lymphoma only stereotaxic biopsy enables a positive diagnosis to be made, but imaging methods, such as CT and MRI, provide data that help guide to a diagnosis which sometimes may be definitive. Suggestive of lymphoma is a single infiltrating lesion wider than 4 cm, which is paraventricular or located in the posterior fossa, has little perilesional alteration and a short tumoral doubling time during the imaging follow-up. Suggestive of toxoplasmosis are multiple, small, annular or nodular lesions with an important perilesional inflammation and usually located in basal ganglia. In addition, in MRI the kinetics of enhancement after contrast injection is intense and occurs early in lymphoma, in contrast with the toxoplasmic abscesses, and this should provide a more specific differential diagnosis. Scintigraphic studies with somatostatin or positron emission tomography, using fluorodeoxyglucose (FDG-PET scintigraphy), also seem to be an interesting mean of making a specific diagnosis of cerebral lesion, according to a principle that is close to dynamic MRI. In lymphoma, capturing of the tracer is about 3 times greater than in infective lesions, notably the toxoplasmic ones. Imaging, therefore, is provided with tools which permit an increasingly specific approach to the primary cerebral lymphoma of AIDS, the definitive diagnosis of which rests on stereotaxic biopsy. This high specificity facilitates a better selection of patients requiring this procedure and shortens the delay in its execution.
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PMID:[The diagnosis of primary cerebral lymphoma in AIDS. The contribution of imaging]. 747 39

Patients with Hodgkin's or non-Hodgkin's lymphoma are staged for treatment based on the extent of known disease involvement and the histopathologic grading of the disease. Radiological techniques, including computed tomography, usually depend on estimates of lymph node enlargement and mass effects as the criterion for disease involvement. Lymphomatous tissue obtained at surgery has shown high-density somatostatin receptors. Several groups have evaluated the utility of 111In-DTPA-pentetreotide (Octreoscan, Mallinckrodt, St. Louis, MO) to detect lymphomatous tissue for more accurate staging of patients with lymphoma. The procedure is safe; both Hodgkin's and non-Hodgkins disease involvement is identified. The results, however, have not been uniformly predictive of disease involvement. Consequently, the routine use of this technique in place of currently used anatomic imaging methods is not recommended at this time. The significance of detecting somatostatin receptors in vivo in patients with malignant lymphoma requires further study.
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PMID:Somatostatin-receptor imaging in lymphoma. 757 45

The role of cytoskeletal microtubules and microfilaments in modulating cAMP generation in S49 lymphoma cells was investigated using the agents colchicine and cytochalasin B, respectively, which are known to disrupt these structures. A 1-hr pretreatment of S49 cells with 10 microM colchicine typically enhanced maximal isoproterenol-(beta-adrenergic receptor) stimulated cAMP accumulation by 100%, whereas cytochalasin B increased isoproterenol-stimulated cAMP by 30%. The combination of colchicine and cytochalasin B synergistically enhanced agonist-stimulated cAMP to 225% over control values. A synergistic increase in cAMP accumulation was also observed in cells treated with the agonist prostaglandin E1 or cholera toxin (which activates the stimulatory guanine nucleotide regulatory (Gs) protein). Colchicine and cytochalasin B did not ablate the inhibitory effects of somatostatin or the stimulatory effect of pertussis toxin treatment on beta-receptor-stimulated cAMP accumulation, indicating that these cytoskeletal disrupting agents do not enhance responsiveness in S49 cells via alterations in the inhibitory guanine nucleotide regulatory protein pathway. Moreover, colchicine, but not cytochalasin B treatment, enhances expression of isoproterenol-promoted 3H-forskolin binding in intact cells (a measure of Gs/adenylyl cyclase coupling). Thus, colchicine and cytochalasin B appear to enhance signaling in the Gs/adenylyl cyclase pathway by alterations of components distal to hormone receptors, most likely at the Gs protein and/or via cAMP generation. These results imply that microtubules and microfilaments can interact in the regulation of this pathway and that increases in cellular cAMP may contribute to the action of drugs that alter function of these cytoskeletal elements.
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PMID:Colchicine and cytochalasin B enhance cyclic AMP accumulation via postreceptor actions. 763 57

We report a case of non-Hodgkin lymphoma presenting as a painless mass of the quadriceps femoris muscle that was detected by a somatostatin analogue (octreotide) scintigraphy. We review the few reported cases of primary muscular lymphoma and discuss the potential value of octreotide imaging as a new diagnostic tool.
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PMID:A rare case of primary skeletal muscle lymphoma: the value of octreotide scintigraphy. 764 18

Cyclic AMP (cAMP) regulates many important physiological processes. Barbiturates influence cAMP regulation, possibly through effects on G proteins. This study used intact S49 mouse lymphoma cells to characterize the role of G proteins in the effect of barbiturates on cAMP regulation. cAMP accumulation was determined in intact S49 WT (wild-type) and S49 cyc- cells (the Gs alpha-deficient mutant) by measuring the conversion of [3H]-ATP to [3H]cAMP in cells preloaded with [3H]adenine. Pentobarbital enhanced cAMP accumulation in WT cells in the absence (basal) or presence of isoproterenol but had no effect on the EC50 for isoproterenol. This effect was dose dependent with a 50-60% enhancement at 2 mM pentobarbital. Pentobarbital did not affect forskolin-stimulated cAMP accumulation in WT cells. In cyc- cells, basal and forskolin-stimulated cAMP accumulation were stimulated only at the highest concentration of pentobarbital used (2 mM). Pentobarbital did not affect the inhibition of cAMP accumulation by somatostatin in WT cells, and pertussis toxin treatment of WT cells did not affect the action of pentobarbital on cAMP accumulation. Pentobarbital did not affect isoproterenol-stimulated adenylyl cyclase activity in whole-cell homogenates or membranes prepared from WT cells. The S-(-)-isomer of pentobarbital enhanced isoproterenol-stimulated cAMP accumulation more than the R-(-)-isomer. Phenobarbital and barbituric acid did not enhance isoproterenol-stimulated cAMP accumulation, whereas the anesthetic barbiturates hexobarbital, pentobarbital, and thiopental all enhanced activity. These results suggest that pentobarbital enhances cAMP accumulation in intact WT cells by a mechanism that is dependent on Gs alpha but independent of Gi.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anesthetic barbiturates enhance Gs alpha-dependent cyclic AMP production in S49 mouse lymphoma cells. 776 36

Helicobacter pylori is a microaerophilic bacterium initially found in the gastric antrum of patients with peptic ulcer disease. As a result, H. pylori is now believed to have a pathophysiologic role in gastritis as well as in peptic ulcer disease. Several recent studies showed that it may be associated with duodenal ulcer relapse and that eradication therapy using antibiotics may significantly decrease the ulcer recurrence rate in duodenal ulcer patients. Moreover, epidemiological studies suggest that it may increase the relative risk of carcinoma in the stomach and preliminary studies seem to indicate that some low-grade lymphoma in the stomach may regress after H. pylori eradication. Although the mechanisms by which H. pylori induces mucosal injury and/or neoplasm is not clearly understood, several modifications in gastric functions have been reported. The most specific way of detecting H. pylori in tissue is a combination of culture and histologic staining of mucosal biopsy specimens obtained by endoscopy. Rapid urease test, cytology and PCR procedures performed on biopsies may give rapid, sensitive and specific results. Breath test using 13C- or 14C-radiolabelled urea and serology tests are of particular importance when H. pylori diagnosis is needed via no invasive procedures. Helicobacter pylori is supposed to interact with G and D cells. Gastrin and somatostatin are synthetized and released from antral G and gastric D cells respectively. The gastric D cells are in close contact with either G and parietal cells. Gastrin stimulates gastric acid secretion and epithelial gastric cell proliferation (parietal and EC-L cells) while somatostatin inhibits these effects. Chronic gastritis is associated with fundic duodenal ulcer disease. In this situation, basal gastrin and meal- or bombesin-stimulated gastrin in the serum (especially gastrin G17) have been found to be higher in H. pylori positive than in negative patients. Moreover, gastrin decreases up to normal levels after eradication of H. pylori. The long term effect of a such hypergastrinemia is not so far established. The mechanism underlaying hormonal modification is poorly understood. Since no G/D cell ratio modification could be found after H. pylori eradication while the amount of somatostatin increases, one would suggest functional alteration of either G or D cells in the H. pylori-related chronic gastritis. The role of inflammatory mediators on the gastrin release and the processing of progastrin induced by the bacterium need further investigations.
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PMID:[Helicobacter pylori, a rediscovered bacterium. Implication in gastroduodenal diseases]. 789 50

Normal as well as activated lymphocytes, macrophages and leukaemic cells have previously been shown by radio receptor analysis to express receptors for somatostatin. An 111In labelled somatostatin analogue was already used successfully in the visualization of a variety of neuro-endocrine tumours. We investigated 10 consecutive patients with malignant lymphomas (Hodgkin's disease and non-Hodgkin's lymphomas). In all patients the lymphoma deposits could be visualized with somatostatin receptor imaging. In four patients additional tumour localizations were observed as compared to the results of combined physical and radiological (CT and ultrasound) examinations. In four cases tissue biopsies were taken and confirmed by autoradiography to be somatostatin receptor positive. These data indicate that malignant lymphomas may express somatostatin receptors in sufficient numbers and density to allow in vivo tumour visualization with a radiolabelled somatostatin analogue.
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PMID:Somatostatin analogue scintigraphy of malignant lymphomas. 809 27


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