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)

Substance P (sP) and Somatostatin (SOM), so as other neuropeptides can modulate neurologic and immunologic functions. sP has been described to enhance both in vitro and in vivo immunoglobulin synthesis. On the contrary, SOM has an inhibitory effect on the same activity. The modulating effect is more evident on IgA isotype. Hypergammaglobulinemia and in particular high levels of IgA is a common finding in pediatric AIDS and an imbalance among regulatory effects of neuropeptides might be suggested. In order to evaluate the plasma levels of sP in pediatric AIDS we studied 15 children with HIV infection (status P2), 10 seronegative children born to HIV positive mothers and 10 healthy children of the same age. All the HIV positive children had high plasma levels of IgG and IgA. The plasma level of sP was extremely higher in HIV positive children while no significant difference was found between seronegative children born to HIV positive mothers and healthy children. SOM was decreased in HIV positive children when compared to control groups but a significant difference was not reached. It might be supposed that HIV infection, through a dysregulation among neuropeptides interferes on immune functions and in particular on IgA synthesis. On the other hand it might be suggested that the imbalance between sP and SOM depends on the viral infection of immune cells since it has been demonstrated that SOM and other neuropeptide are synthesized by lymphoid tissue. Further studied relevance of neuropeptide disorders in pediatric AIDS.
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PMID:[Changed levels of substance P and somatostatin in HIV-positive children]. 128 55

The multiple actions of somatostatin are mediated by specific membrane-bound receptors present in all somatostatin target tissues, such as brain, pituitary, pancreas, and gastrointestinal tract. Three different types of tissues in the human gastrointestinal tract express somatostatin receptors: (1) the gastrointestinal mucosa, (2) the peripheral nervous system, and (3) the gut-associated lymphoid tissue, where the receptors are preferentially located in germinal centers. In all these cases, somatostatin binding is of high affinity and specific for bioactive somatostatin analogs. Somatostatin receptors are also expressed in pathological states, particularly in neuroendocrine tumors of the gastrointestinal tract. Ninety percent of the carcinoids and a majority of islet-cell carcinomas, including their metastases, usually have a high density of somatostatin receptors. Only 10 percent of the colorectal carcinomas and none of the exocrine pancreatic carcinomas, however, contain somatostatin receptors. The somatostatin receptors in tumors are identified with in vitro binding methods or with in vivo imaging techniques; the latter allow the precise localization of the tumors and their metastases in the patients. Since somatostatin receptors in gastroenteropancreatic tumors are functional, their identification can be used to assess the therapeutic efficacy of octreotide to inhibit excessive hormone release in the patients.
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PMID:Somatostatin receptors in the gastrointestinal tract in health and disease. 134 64

Somatostatin receptors were evaluated in four human gut-associated lymphoid tissues (palatine tonsils, ileal Peyer patches, vermiform appendix, and colonic solitary lymphatic follicles) using receptor autoradiography on tissue sections incubated with 125I[Tyr3]octreotide. All four tissues were somatostatin-receptor positive; the receptors were preferentially located in the germinal centers, with the luminal part of the center more strongly labeled than the basal part. The corona of the follicles and the primary follicles without germinal centers did not display somatostatin receptors. The receptors were of high affinity (Kd = 1.3 +/- 0.6 nmol/L) and specific for somatostatin. Displacement by nanomolar concentrations of somatostatin 14, somatostatin 28, and octreotide was observed, as was guanosine triphosphate dependency. The gastrointestinal mucosa and the plexus submucosus and myentericus also contained somatostatin receptors. These data strongly suggest that the germinal centers of the gut-associated lymphoid tissue are a site of action of somatostatin. It possibly mediates antiproliferative effects and inhibits immunoglobulin synthesis in the activated lymphoid cells. The human gut represents a multifaceted target for somatostatin action, in which at least three different tissues (mucosa, nerve plexus, and lymphoid tissue) are involved.
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PMID:Preferential location of somatostatin receptors in germinal centers of human gut lymphoid tissue. 135 71

We evaluated the presence of anterior pituitary hormones; follicle-stimulating hormone (FSH) and its beta-subunit (beta-FSH), luteinizing hormone (LH) and its beta-subunit (beta-LH), beta-subunit of thyroid-stimulating hormone (beta-TSH), adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL); the placental hormone human chorionic gonadotropin (hCG); and somatostatin, in paraffin and frozen sections of the human thymus. Epithelial cells in the medulla were immunoreactive for most of these hormones, in varying density and intensity of labeling. The cells labeled varied from epithelial cells surrounding Hassall's corpuscles toward solitary cells or small epithelial aggregates in the medulla. FSH immunoreactivity did occur predominantly in epithelial cells of the cortex, in apparent contrast to the predominant medullary location of cells immunolabeled for beta-FSH. The epithelial nature of FSH-immunoreactive cells was confirmed by two-color immunohistochemistry with anti-keratin antibody. In addition to FSH, some epithelial cells in subcapsule and cortex were labeled by antibodies to beta-FSH, beta-LH, beta-TSH, ACTH, GH, and PRL. Some macrophage-like cells surrounded by a rosette of lymphocytes were immunoreactive for FSH and GH. Some interdigitating reticulum-like cells were labeled by anti-beta-LH. Immunolabeling of lymphocytes was found for hCG, especially lymphocytes in the medulla. Two-color immunohistochemistry with anti-CD3 revealed a strong CD3 expression on hCG-immunoreactive cells, whereas CD3-negative cells were hCG-negative. T cells immunolabeled for hCG were also found in peripheral lymphoid organs.
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PMID:The neural and neuro-endocrine component of the human thymus. II. Hormone immunoreactivity. 139

Because several peptides originally found in the pituitary as within the central nervous system have been localized in lymphoid tissues and because somatostatin (somatotropin-release-inhibiting hormone, SRIH) can act on cells of the immune system, we searched for this peptide in lymphoid organs. We demonstrated that SRIH mRNA exists in lymphoid tissue, albeit in smaller levels than in the periventricular region of the hypothalamus, the brain region that contains the highest level of this mRNA. SRIH mRNA was found in the spleen and thymus of male rats and in the spleen, thymus, and bursa of Fabricius of the chicken. Its localization in the bursa indicates that the peptide must be present in B lymphocytes since this is the site of origin of B lymphocytes in birds. The SRIH concentration in these lymphoid organs as determined by radioimmunoassay was greater in the thymus than in the spleen of the rat. These concentrations were 50 times less than those found in the periventricular region of the hypothalamus, the site of the perikarya of SRIH-containing neurons. In the chicken, as in the rat, the concentration of SRIH was greater in the thymus than in the spleen; it was present in the bursa of Fabricius, also in higher concentration than in the spleen. Fluorescence immunocytochemistry revealed the presence of SRIH-positive cells in clusters inside the white pulp and more dispersed within the red pulp of the spleen of both the rat and the chicken. The thymus from these species also contained SRIH-positive cells within the medulla and around the corticomedullary junction. In the chicken, there were large clusters of SRIH-positive cells in the medullary portion of each nodule of the bursa of Fabricius. Preabsorption of the primary antiserum or replacing this antiserum with normal rabbit serum verified the specificity of staining. Sequential immunostaining of the same sections from rat spleen using first SRIH antibody and subsequently a monoclonal antibody against a rat B-cell surface antigen revealed the presence of SRIH immunoreactivity in some, but not all, B cells. Other cell types in spleen not yet identified also stained positively with the SRIH antibody but were not reactive to monoclonal antibodies to rat Thy-1.1, a marker for all the thymic T lymphocytes. The possibility that SRIH is present in other populations of cells in the spleen cannot be ruled out. Sequential immunostaining of the same sections of rat thymus revealed the presence of SRIH immunoreactivity in a small population of T lymphocytes in the medulla, as revealed by the Thy-1.1 marker. The SRIH-positive cells were nonimmunoreactive when exposed to the B-cell marker; however, the possibility that SRIH is present in other cells was not investigated. Thus, our results indicate that SRIH is synthesized and stored in cells of the immune system. SRIH may be secreted from these cells to exert paracrine actions that alter the function of immune cells in spleen and thymus.
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PMID:Evidence that somatostatin is localized and synthesized in lymphoid organs. 168 64

A correlative immunohistochemical and stereological study of neuroendocrine cells (NEC) was carried out in the antrum of twenty human fetuses with gestational ages from 18 to 42 weeks and of two specimens postnatally. Neuron-specific enolase (NSE) as a common marker of neurons and NEC, as well as gastrin (G-) and somatostatin (D-) immunoreactive cells served for evaluation of volume density, which proved to be the most convenient method for quantitative analysis of NEC. It was observed that a considerable frequency of NEC appeared at 23-24 weeks of gestation (8% of NSE- and 6% of G- cells) and coincided with the adult pattern of intramural innervation. After a repeated increase of NEC in the 26-week-old fetus, the frequency of NEC remained persistant during the perinatal period (10-12% of NSE- and 7-8% of G- cells). An exception was a specimen with a prolonged pregnancy (42 weeks) in which the percentage of NSE- (17%) and G- (10%) cells was almost the same as at 6 weeks postnatally. The maximal quantitative difference of NEC was noted between 6- and 8-week specimens postnatally, e.g. 9% to 22% of G- cells, respectively. Observations obtained by NSE and S-100 protein were also demonstrated in lymphoid cells of gut associated and mesenteric lymphoid tissue.
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PMID:Immunohistochemical and stereological study of neuroendocrine cells in human antrum during the perinatal period. 168 59

In the present work we demonstrate immunohistochemically the presence of both immunoreactive vasoactive intestinal peptide (IR-VIP) and immunoreactive somatostatin (IR-SOM) cells in the thymus of neonatal and adult rats. IR-VIP and IR-SOM from thymic tissue extracts were identified by gel chromatography, HPLC as VIP standard, and somatostatin S-28, respectively. IR-VIP (352.7 pg/thymus) amounts greater than those of IR-SOM (38.7 pg/thymus) detected by radioimmunoassay in the thymus of 3-month-old rats reflected the abundance of IR-VIP positive cells demonstrated by immunohistochemistry. Somatostatin-like immunoreactive cells were identified as epithelial or neuroendocrine-like cells arranged in the thymic cortico-medullary border, whereas IR-VIP positive cells appeared to be large lymphoid cells distributed along the connective tissue trabeculae. Furthermore, IR-VIP lymphoid cells occurred in the periarteriolar lymphoid tissue of the splenic white pulp where lymphoblasts accumulate. The results are discussed with respect to the mutual interactions between the neuroendocrine and immune systems and the possible role played by neuropeptides in these interactions.
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PMID:Demonstration of immunoreactive vasoactive intestinal peptide (IR-VIP) and somatostatin (IR-SOM) in rat thymus. 197 6

Several peptides originally described as neurotransmitters or gut hormones have recently been shown to modulate the immune response. Three of these peptides, vasoactive intestinal peptide, substance P, and somatostatin, regulate the function of immune effector cells in gut-associated lymphoid tissue. Vasoactive intestinal peptide modulates lymphocyte migration and natural killer cell activity by a cyclic adenosine monophosphate (cAMP)-dependent mechanism, whereas substance P induces mediator release by a cAMP-independent mechanism. Somatostatin antagonizes the effects of both vasoactive intestinal peptide and substance P by a mechanism that appears to involve inhibitory guanine nucleotide binding proteins. Neuropeptide regulation of immune cells in gut-associated lymphoid tissue may thus play an important role in gastrointestinal physiology.
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PMID:Neuropeptides and gastrointestinal immunity. 243 82

The neuropeptides vasoactive intestinal peptide (VIP), substance P, and somatostatin are found in high concentrations in both the central nervous system and the gastrointestinal tract. Specific high affinity receptors for VIP, substance P and somatostatin have been identified on both human and murine lymphocytes, suggesting a role for each of these neuropeptides in a neuroimmune axis. These peptides may be important modulators of mucosal immunity regulating lymphocyte proliferation and trafficking in gut associated lymphoid tissue, synthesis of IgA, and histamine release. Somatostatin antagonism of both VIP and substance P effects has been observed in the immune system. Though the mechanisms by which these neuropeptides modulate immune function have not been completely delineated, current evidence supports the hypothesis that VIP modulates immune function via cAMP dependent pathways while substance P regulation of the immune response involves phospholipid metabolism. Somatostatin inhibition of both cAMP dependent and phospholipid dependent effects has been documented in endocrine tissues. Delineation of the role of these peptide-peptide interactions in modulation of the immune response promises to be a fruitful area for further investigation.
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PMID:Neuropeptide modulation of the immune response in gut associated lymphoid tissue. 245 49

Previous work has established that the central nervous system can modulate the immune response. Direct routes through which this regulation may occur are the sympathetic and sensory innervation of lymphoid organs. We investigated the innervation of canine mesenteric lymph nodes using immunohistochemistry and the expression of binding sites for sensory neuropeptides using quantitative receptor autoradiography. The sympathetic innervation of lymph nodes was examined by immunohistochemical methods using an antiserum directed against tyrosine hydroxylase (TOH), the rate limiting enzyme in catecholamine synthesis. TOH-containing fibers were associated with 90% of the blood vessels (arteries, veins, arterioles and venules) in the hilus, medullary and internodular regions of lymph nodes and in trabeculae with no obvious relationship to blood vessels. The sensory innervation of lymph nodes was investigated using antisera directed against the putative sensory neurotransmitters calcitonin gene-related peptide (CGRP) and substance P (SP). CGRP- and SP-containing fibers were detected in the hilus, the medullary region, and the internodular region of lymph nodes usually in association with arterioles and venules. About 50% of the arterioles and venules exhibited a CGRP innervation and a smaller fraction (5-10%) were innervated by SP-containing fibers. Few if any TOH, CGRP, and SP nerve fibers were detected in the germinal centers of lymph nodes. Using quantitative receptor autoradiography we studied the distribution of receptor binding sites for the sensory neuropeptides CGRP, SP, substance K (SK), vasoactive intestinal peptide (VIP), somatostatin (SOM), and bombesin. Specific CGRP binding sites were expressed throughout lymph nodes by trabeculae, arterioles, venules and 25% of the germinal centers. SP receptor binding sites were localized to arterioles and venules in the T cell regions and 25-30% of the germinal centers. VIP binding sites were localized to the internodular and T cell regions, to medullary cords, and to 10-20% of germinal centers. SK, SOM, and bombesin binding sites were not detected in the lymph nodes, although receptor binding sites for these peptides were detected with high specific/nonspecific binding ratios in other canine peripheral tissues. Taken together with previous results these findings suggest that the sympathetic and sensory innervation of mesenteric lymph nodes appears to be involved with the regulation of their blood and lymph flow. The neuropeptide receptor binding sites in lymph node germinal centers may be expressed by lymphocytes upon activation by antigens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The localization of sensory nerve fibers and receptor binding sites for sensory neuropeptides in canine mesenteric lymph nodes. 245 53


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