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)

Regulatory peptides, such as vasoactive intestinal peptide (VIP), somatostatin (SS), or substance P (SP), are considered to play a role in immune regulation. To localize the targets of these peptides in the human immune system, their receptors have been evaluated with in vitro receptor autoradiography in lymph nodes, tonsils, appendix, Peyer's patches, spleen, and thymus. The three peptide receptors were detected in all lymphoid tissues tested, but, unexpectedly, usually in distinct compartments. In lymph nodes, palatine tonsils, vermiform appendix, and Peyer's patches, VIP receptors were found in the CD3 positive zone around lymphoid follicles; SS receptors in the germinal centers of secondary follicles; and SP receptors mainly in interfollicular blood vessels. In the spleen, VIP receptors were detected in periarterial lymphatic sheaths, SS receptors in the red pulp, and SP receptors in the central arteries. In the thymus, VIP receptors were present in cortex and medulla, SS receptors in the medulla, and SP receptors in blood vessels. For comparison, cholecystokinin (CCK)-A and -B receptors were not demonstrated in any of these tissues. These results suggest a strong compartmentalization of the three peptide receptors in human lymphoid tissues and represent the molecular basis for the understanding of a very complex and interactive mode of action of these peptides.
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PMID:Localization of receptors for vasoactive intestinal peptide, somatostatin, and substance P in distinct compartments of human lymphoid organs. 963 16

The autonomic nervous system plays a significant role in liver physiology and pathology. The aim of the present study was to investigate peptidergic nerve fibres in the liver of patients with malignant gastrointestinal tumors that are not metastasizing in this organ. Using light and electron microscopic immunohistochemistry, somatostatin (SOM)-, neuropeptide Y (NPY)-, substance P (SP)- and calcitonin gene-related peptide (CGRP)-immunoreactive (IR) nerve fibres (NF) were detected in the portal tract and perisinusoidally. Histologically, the liver showed dilated sinusoids, filled with lymphoid cells, and scarcely marked perisinusoidal fibrosis. Neuropeptide-IR NF were found in close contact with hepatic sinusoids. Numerous IR varicosities were detected in the sinusoidal wall. We discuss the origin and role of these NF in the liver. Probable quantitative changes in peptidergic NF ensue the inflammatory reaction in sinusoids in malignant gastrointestinal tumors. This could also reflect the increased exposure of the liver to toxic substances in the portal blood flow.
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PMID:Peptidergic nerve fibres in the human liver. 971 62

Somatostatin (SS) was originally described as a growth hormone release inhibiting factor synthesised in the hypothalamus. Recently, SS and its receptor (SSTR) have been demonstrated in lymphoid tissues and seem to play a regulatory, largely inhibitory, role in immune responses. The aim of the present study was to check the immunosuppressive effect of a SS derived peptide, the octreotide (SMS 201-995) and to verify whether this molecule acted synergistically with FK506. An immunosuppressive effect of SMS was observed on the proliferation of rat spleen cells induced in vitro, either by polyclonal mitogens such as PHA or by alloantigens. With PHA stimulation, 10(-14) M SMS significantly enhanced the immunosuppressive action of 0.00001 microg/ml FK506. The addition of SMS in MLR (10(-11)-10(-9)M) increased the antiproliferative effect of both 0.0001 microg/ml and 0.00001 microg/ml FK506. In consideration of the extremely low concentration of both drugs that was required to obtain a good immunosuppression in vitro, we verified the association of FK506 and SMS in vivo in an allogeneic skin graft model that used Lewis (Lew) rats as donors and Brown Norway (BN) rats as recipients. BN treated with 0.1 mg/kg FK506 and 0.5-10 microg/kg SMS showed a significant increase in mean skin allograft survival time when compared to either a monotherapy or control group. None of the animals died or showed signs of drug-related toxicity. In conclusion, a combined therapy of SMS and FK506, administered at lower dosages than those that are considered therapeutic, led to an effective immunosuppression without any undesirable side effects.
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PMID:Evidence that SMS 201-995 enhances the immunosuppressive effect of FK506. 981 92

Integrins play an important role in lymphocyte adhesion to cellular and extracellular components of their microenvironment. The regulation of such adhesion often involves changes in the functional state of the integrins rather than alterations in their expression levels. Although the functional basis for such transitions is unknown, a possible role for disulfide exchange might be postulated based on the observations that integrin function can be activated by bifunctional reducing agents or by Abs that react with areas adjacent to predicted long-range disulfide bonds in integrins. Recently, it has been reported that enzymes that catalyze disulfide exchanges such as protein disulfide isomerase (PDI) are present on the surface of lymphoid cells, raising the possibility that such enzymes might be involved in the control of lymphocyte adhesion. A number of inhibitors of PDI function were examined for their effects on integrin-mediated adherence of T cells. The results did not support role for PDI in the regulation of integrin function, as the inhibitors somatostatin A, tocinoic acid, dithiobisnitrobenzoic acid, and anti-PDI mAb did not interfere with adherence. However, one of the PDI inhibitors, bacitracin, selectively interfered with the beta1 integrin-mediated adherence of lymphoid cells to collagen, fibronectin, laminin, and VCAM-1, and with alpha4beta7-dependent adherence to fibronectin and to VCAM-1. In contrast, alpha(v)beta3- and alpha(L)beta2-mediated adherence were not inhibited. Thus, it appears that bacitracin may be a selective inhibitor of beta1 and beta7 integrin functions by an as yet unknown mechanism.
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PMID:The selective inhibition of beta 1 and beta 7 integrin-mediated lymphocyte adhesion by bacitracin. 983 22

Somatostatin is a neuropeptide that is widely distributed throughout the body. It acts as a neurohormone and a neurotransmitter and may also have an immunomodulatory role. The genes for five subtypes of somatostatin receptors (sst) have been cloned, suggesting that the diverse effects of the peptide might be mediated by different receptors. We are interested in studying the role of sst ininflammation, using an animal model. Because of the up-regulation of sst expression in inflamed joints in human rheumatoid arthritis, we chose rat adjuvant arthritis as an experimental model. In order to determine which of the sst subtypes might be important in immune modulation, subtype expression in leukocytes isolated from different lymphoid tissues of the rat was studied. Also, the expression levels of the most abundantly expressed sst mRNAs in leukocytes from spleen and blood were compared in rats with adjuvantarthritis and controls, using a semi-quantitative approach. Furthermore, the effect of systemic administration of a long-acting somatostatin analogue, octreotide, which binds selectively to sst subtypes 2 and 5 (sst2 and sst5), on the incidence and the severity of rat adjuvant arthritis, was studied. The main sst expressed in cells of the rat immune system, both resting and activated, were found to be sst3 and sst4. This contrasts with the human and murine situations, in which sst2 appears to be the main subtype expressed in the immune system. No quantitative differences in sst subtype mRNA levels in leukocytes from spleen and blood were found between rats with adjuvant arthritis and controls. Finally, no effect of systemic administration of octreotide on either the incidence or severity of adjuvant arthritis in Lewis rats was found. As octreotide binds selectively to sst2 and sst5, the absence of an immunomodulatory effect of this analogue in rat adjuvant arthritis corroborates our finding that these sst subtypes are not expressed in cells of the rat immune system. In conclusion, cells of the rat immune system appear to express a spectrum of sst (sst3 and sst4) different from that found in human granulomatous and autoimmune disease (mainly sst2). Therefore, the rat adjuvant arthritis model appears to be suitable only for studying the immunomodulatory effects of somatostatin analogues which have a high affinity for sst3 and sst4, but not for studying the immunomodulatory effects of octreotide, which has a high affinity only for sst2 and sst5.
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PMID:Somatostatin receptor subtype expression in cells of the rat immune system during adjuvant arthritis. 1019 40

The relationship of Helicobacter felis, an organism that is observed in the stomachs of dogs, to gastric disease in dogs is unclear. The objective of this study was to determine if Helicobacter felis infection alters gastric morphology and gastric secretory function in dogs. Five specific-pathogen-free (SPF), Helicobacter-free Beagle dogs were examined before and for 26 weeks after inoculation with H. felis (ATCC 49179). Three SPF uninfected dogs served as controls. All five dogs became colonized by H. felis as determined by urease activity, histopathology, polymerase chain reaction, and transmission electron microscopic examination of serial gastric biopsies. The degree of colonization ranged from < 1 organism/400 x field to > 10 organisms/400 x field. The fundus, body, and cardia were most heavily colonized. Evaluation of gastric biopsies showed mild gastric inflammation and lymphoid follicles in both infected and uninfected dogs. There was no correlation between the number of organisms observed and the degree of gastric inflammation or number of lymphoid follicles. The gastric secretory axis, assessed by fasting and meal-stimulated plasma gastrin, mucosal gastrin and somatostatin immunoreactivity, fasting gastric pH, and pentagastrin-stimulated gastric acid secretion, was similar in both infected and uninfected dogs. Fasting gastric pH was not a reliable indicator of gastric secretory function. These findings suggest that H. felis may not be a gastric pathogen in dogs. However, the density of colonization and limited duration of infection should be considered when interpreting these findings.
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PMID:Helicobacter felis infection in dogs: effect on gastric structure and function. 1033 32

During the last decade the concept of a narrow communication between the immune and classical neuroendocrine systems has been supported by cumulative evidence. One of the common links between the two systems is formed by the production of somatostatin (SS), the presence of SS receptors (SS-R) and the functional effects of SS on both endocrine and immune cells. While in the endocrine system SS-R activation is coupled to mainly inhibitory effects, both inhibitory and stimulatory effects of SS have been demonstrated on the function of immune cells (ie proliferation and secretion). Moreover, in contrast to endocrine cells (ie growth hormone (GH)-secreting pituitary cells) in which SS and its analogues inhibit GH secretion in the nanomolar range in a dose-dependent manner achieving maximal inhibitory effects at higher concentrations, biphasic effects of SS are generally found on the function of immune cells with inhibition at low (nanomolar) concentrations and absence of an effect at higher (micromolar) concentrations. Neuroendocrine cells often express multiple SS-R subtypes, which may be linked to specific functions. Scarce information is available so far on the SS-R subtype expression pattern as well as on the second messenger systems linked to SS-R activation in human lymphoid cells. The recent development of novel SS-R subtype-selective SS analogues will be helpful in unravelling the functional roles of the individual SS-R subtypes in SS-R-expressing human neuroendocrine and immune cells.
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PMID:Functional role of somatostatin receptors in neuroendocrine and immune cells. 1057 51

The thymus is the primary lymphoid organ where different factors participate in regulating the proliferation and differentiation of T cells. The thymic epithelium is the main cellular component in driving the maturation of thymocytes through cell-to-cell and extracellular matrix-mediated interactions. Thymic hormones and cytokines play a critical role in the proliferation, differentiation and selection of precursor cells along the T-cell lineage. However, other locally produced hormones and neuropeptides participate in thymic functions in an autocrine and paracrine manner. Some of them have well-characterized actions, whereas somatostatin (SS), although it has been identified, has not been investigated in detail. SS inhibits hormone and exocrine secretion, modulates neurotransmission and inhibits cell proliferation. The biological effects of SS are mediated through five G protein-coupled membrane receptor subtypes (sst1-5). SS receptors (SS-R) have been demonstrated in normal tissues and tumours at the protein and mRNA levels. Sst2 mRNA has been detected in the murine thymus, whereas sst3 and sst4 mRNAs are expressed in the rat immune system. The significance of the presence of specific SS-R subtypes remains to be clarified. Moreover, the activation of lymphoid cells seems to modify their SS-R expression pattern. SS, sst1, sst2A and sst3 mRNAs have been found in normal human thymic tissue, whereas enriched cultured thymic epithelial cells (TEC) selectively express SS, sst1 and sst2A mRNAs. Furthermore, TEC respond in vitro to SS and octreotide by inhibiting cell proliferation. Immunoreactivity for sst2A has been detected primarily in the medulla, where TEC, dendritic cells and macrophages are the major components, in line with the predominant binding of the sst2 receptor-preferring ligand [125I-Tyr3]-octreotide in this region. The heterogeneous distribution of SS-R subtypes on specific cell subsets indicates that SS may play a paracrine and/or autocrine role in regulating cell activities in the thymus.
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PMID:Somatostatin receptors in the thymus. 1057 52

The relationship of Helicobacter felis, a bacterium observed in the stomachs of cats, to gastric disease is unclear. The objective of this study was to determine if H. felis infection alters gastric histopathology, proinflammatory cytokine expression, and secretory function and evokes a humoral immune response in cats. Five specific-pathogen-free (SPF) Helicobacter-free cats were studied before and for 1 year after oral inoculation with H. felis (ATCC 49179). Four SPF H. felis-uninfected cats served as controls. The stomachs of all five H. felis-inoculated cats became colonized, as determined by urease activity, histopathology, PCR, culture, and transmission electron microscopy of serial gastric biopsies at 0, 3, 5, 8, and 12 months. Uninoculated cats remained Helicobacter free. Lymphoid follicular hyperplasia, atrophy, and fibrosis were observed primarily in the pylorus of infected cats. Mild mononuclear inflammation was detected in both infected and uninfected cats, but was more extensive in infected cats, with pangastric inflammation, eosinophilic infiltrates, and cardia gastritis observed only in infected cats. No upregulation of antral mucosal interleukin 1alpha (IL-1alpha), IL-1beta, or tumor necrosis factor alpha was detected by reverse transcription-PCR in any cat. The gastric secretory axes, assessed by fasting plasma gastrin, antral mucosal gastrin and somatostatin immunoreactivity, and pentagastrin-stimulated gastric acid secretion, were similar in both infected and uninfected cats. Gradual seroconversion (immunoglobulin G) was observed in four of five infected cats, with enzyme-linked immunosorbent assay values reaching 4x to 12x baseline 12 months postinfection. These findings indicate that H. felis infection in cats induces lymphoid follicular hyperplasia, mild gastritis, and seroconversion, but is associated with normal gastric secretory function.
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PMID:Helicobacter felis infection is associated with lymphoid follicular hyperplasia and mild gastritis but normal gastric secretory function in cats. 1063 46

Somatostatin receptors are supposed to be important in the regulation of apoptosis. In this study, we measured apoptosis occurring spontaneously, or induced by the synthetic somatostatin analogue, the peptide TT-232. We examined isolated human peripheral blood lymphocytes (PBL) from 32 nurses exposed bedside to cytostatic drugs, 12 chronic lymphoid leukaemia (CLL) patients prior to treatment, and 19 unexposed, healthy donors without anamnestic occupational exposure to genotoxic agents. Cells were stimulated by phytohaemagglutinin-P (PHA) and cultured for 69 h with or without 15 microg/ml TT-232, respectively. Cell kinetic parameters and apoptosis were determined by flow cytometry after staining with FITC-labeled anti-BrdU and propidium iodide (PI) and the results on spontaneous and peptide-induced apoptosis were compared with the obtained chromosome aberration frequencies (CA). The peptide TT-232 unexpectedly induced chromosome breakage in addition to apoptosis. The mean spontaneous apoptotic fractions were 6.65+/-0.89%, 6.46+/-0. 53%, and 3.07+/-0.57%, and the mean CA yields in the samples without TT-232 were 1.74+/-0.46%, 2.44+/-0.40%, and 4.50+/-1.05%, for healthy subjects, nurses, and CLL patients, respectively. A total of 15 microg/ml TT-232 treatment in healthy subjects increased the mean CA frequency (10.38+/-1.57%), as well as the apoptotic cell fraction (2.63+/-0.45 times higher than the corresponding untreated sample). In TT-232-treated PBLs of nurses, CA remained unchanged and the mean apoptotic cell fraction showed only a slight increase (1.24+/-0.11 times higher than the untreated). Among CLL patients, TT-232 treatment significantly increased both CA (up to 17.83+/-4.04%) and the ratio of apoptotic cells (21.78+/-11.00 times higher than the untreated). These results demonstrated significant differences in apoptosis sensitivity in controls, nurses and CLL donors, after 15 microg/ml TT-232 treatment. Data also indicate that the induced CA yields in CLL donors with high CA are in correlation with TT-232-induced apoptosis.
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PMID:The somatostatin analogue peptide TT-232 induces apoptosis and chromosome breakage in cultured human lymphocytes. 1070 70


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