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)

The granulomas of mice infected with Schistosoma mansoni for 8 wk have macrophages that secrete somatostatin 1-14 (SOM). Within the granuloma, SOM has no known function. To uncover the possible significance of SOM produced within this granulomatous inflammation, we sought SOM receptors on distinct cellular components of the granuloma to identify cells targeted for SOM action. [125I]SOM 1-14 bound to dispersed granuloma inflammatory cells specifically and reversibly. Scatchard analysis suggested one receptor type (kDa 4.28 x 10(-9) M). Octreotide, a stable SOM derivative, displaced radioligand (kDa 1.01 x 10(-10) M), but SOM 1-28, substance P, and vasoactive intestinal peptide did not. The SOM receptor localized exclusively to a subset of granuloma CD4+ T lymphocytes. Using IL-5 and IFN-gamma ELISA, it was shown that granuloma T cells can secrete appreciable IL-5 and IFN-gamma when stimulated with Ag or mitogen. Both SOM and octreotide at concentrations as low as 10(-10) M substantially decreased IFN-gamma secretion from Ag or mitogen-stimulated T cells, but at concentrations as high as 10(-6) did not affect IL-5 production. Octreotide administered to animals in vivo decreased the intensity of the granulomatous response. Thus, some granuloma T cells have SOM 1-14 receptors. SOM 1-14, a product of granuloma macrophages, may participate in regulation of the granulomatous response by modulating the secretion of some lymphokines. Octreotide, a clinically useful SOM analog, mimics the action of SOM on the immune system.
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PMID:Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin receptors and respond to somatostatin with decreased IFN-gamma secretion. 135 73

The factors responsible for eosinophil recruitment are poorly defined, although both platelet-activating factor (PAF) and cytokines appear to be involved in regulating this process. We compared eosinophil mobilization induced by PAF or antigen injection in the peritoneal cavity of hypereosinophilic rats and the effects of the PAF antagonist BN 52021, the somatostatin analog BIM 23014, and cyclosporin A on this process. PAF induced a significant increase of both peritoneal and circulating eosinophil count. Cyclosporin A almost totally abrogated these variations, whereas BN 52021 reduced the peritoneal increase. Similarly to PAF, peritoneal antigen challenge in actively sensitized animals increased peritoneal and circulating eosinophil counts. Cyclosporin A abolished both hypereosinophilia and peritoneal eosinophil infiltration. BIM 23014 reduced the circulating eosinophils and cell infiltration. In contrast, BN 52021 primarily decreased peritoneal eosinophil recruitment, while having little effect on circulating cells. The different mechanisms of action of these drugs and the involvement of interleukin 5 in eosinophil recruitment are discussed.
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PMID:Modulation by drugs of eosinophil recruitment induced by immune challenge in the rat. Possible roles of interleukin 5 and platelet-activating factor. 246 17

The effects of vasoactive intestinal peptide (VIP) on human IgA1 and IgA2 production were studied. In unfractionated small resting B cells stimulated with anti-CD40 monoclonal antibody (mAb), VIP induced IgA1 and IgA2 production without affecting the production of IgG1, IgG2, IgG3, IgG4, IgM, or IgE. When small B cells were separated into sIgA1+, sIgA2+, sIgA1- and sIgA2- B cells, anti-CD40 mAb plus VIP induced IgA1 and IgA2 production by surface IgA1- (sIgA1-) and sIgA2- B cells, respectively, while having no effect on sIgA1+ and sIgA2+ B cells. This induction by VIP was specific, since anti-CD40 mAb plus other neuropeptides, i.e., somatostatin or substance P, had no effect, and moreover, the induction was specifically blocked by a VIP antagonist. Further, anti-CD40 mAb plus various cytokines, including interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, transforming growth factor-beta, low molecular weight B cell growth factor, and interferon-gamma, did not induce IgA1 and IgA2 production by sIgA1- and sIgA2- B cells, respectively. These results indicate that in the presence of anti-CD40 mAb, VIP induces IgA1 and IgA2 production by isotype switching.
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PMID:Vasoactive intestinal peptide specifically induces human IgA1 and IgA2 production. 752 70

We studied the effects of vasoactive intestinal peptide (VIP) on IgA1 and IgA2 production in human fetal B cells and pre-B cells derived from bone marrow. VIP induced IgA1, IgA2, and IgM production in sIgM+, CD19+ fetal B cells stimulated with anti-CD40 monoclonal antibody (MoAb) without inducing the production of IgG1, IgG2, IgG3, IgG4, or IgE. The anti-CD40 MoAb plus VIP also induced IgA1, IgA2, and IgM production in sIgM-, CD19+ pre-B cells, which was enhanced by the addition of interleukin-7 (IL-7). This induction by VIP was specific, as the anti-CD40 MoAb plus other neuropeptides [ie, somatostatin (SOM) or substance P (SP)] had no effect, and moreover, the induction was specifically blocked by a VIP antagonist. Furthermore, the anti-CD40 MoAb plus various cytokines, including IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, transforming growth factor beta (TGF-beta), low-molecular-weight B-cell growth factor (BCGF), and interferon-gamma (IFN-gamma), did not induce IgA1 and IgA2 production in fetal B cells or pre-B cells. These findings indicate that, in the presence of costimulators, VIP may induce IgA1 and IgA2 production by isotype switching.
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PMID:Induction of IgA1 and IgA2 production in immature human fetal B cells and pre-B cells by vasoactive intestinal peptide. 753 91

Schistosomiasis mansoni is a disease characterized by liver and intestinal granulomas. Previous investigations in our laboratory showed that nylon wool-adherent CD4+ T lymphocytes isolated from murine hepatic schistosome granulomas express receptors for somatostatin 1-14. Moreover, somatostatin 1-14 substantially decreased IFN-gamma and IgG2a, but not IL-5 secretion by dispersed granuloma cells. This paper extends these observations by defining the somatostatin receptor (SSTR) isoform most likely expressed by granuloma inflammatory lymphocytes. Amplification of mRNA by reverse transcription PCR shows SSTR1, SSTR2, and SSTR3 mRNA in normal mouse brain and other tissues. Nevertheless, only the SSTR2 PCR product was amplified from granuloma cell RNA. The nucleotide sequence of the granuloma SSTR2 PCR product from inflammatory cells is identical to the CBA murine brain SSTR2 cDNA sequence. Granuloma-derived T cell lines, FACS-isolated granuloma CD4+ T cells, thymocytes, splenocytes, and cloned T cell lines all contain mRNA for SSTR2 by reverse transcription PCR. Moreover, both SSTR2A and the splice variant SSTR2B can be amplified from dispersed granuloma cells, granuloma T cell lines, thymocytes, and splenocytes. This is the first demonstration that inflammatory cells produce mRNA for an authentic somatostatin receptor. It is probable that the lymphocyte SSTR2 receptor mediates somatostatin-induced modulation of IFN-gamma secretion.
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PMID:T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA. 791 11

The effects of vasoactive intestinal peptide (VIP) on human immunoglobulin (Ig) production were studied in (1) B cell lines; (2) anti-CD40 mAb-stimulated B cells from non-atopic donors; and (3) unstimulated mononuclear cells from atopic patients. In B cell lines, GM-1056, IM-9, and CBL, VIP enhanced IgA1, IgG1 and IgM production, respectively, in a dose-dependent fashion, while the other neuropeptides somatostatin (SOM) or substance P (SP) failed to do so. Among the various cytokines examined including IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, and G-CSF. IL-6 and IL-10 also enhanced Ig production. However, VIP-induced enhancement of Ig production was specific, and was not mediated via these cytokines, since enhancement was blocked by the VIP antagonist, while SOM and SP antagonists, anti-IL-6 mAb, or anti-IL-10 Ab failed to do so. In anti-CD40 mAb-stimulated B cells from nonatopic donors, VIP selectively induced IgA1 and IgA2 production without affecting IgG1, IgG2, IgG3, IgG4, IgM, or IgE production. This stimulatory effect was specifically blocked by the VIP antagonist, but not by SOM or SP antagonists, anti-IL-5 mAb, anti-IL-10 Ab, or anti-TGF-beta Ab. VIP induced IgA1 and IgA2 production by surface IgA1- (sIgA1-) and sIgA2-B cells, respectively, while this agent had no effect on sIgA1+ and sIgA2+B cells. In contrast, in unstimulated mononuclear cells from atopic patients, VIP selectively inhibited spontaneous IgE and IgG4 production without affecting IgG1, IgG2, IgG3, IgM, IgA1, or IgA2 production. This inhibitory effect was specifically blocked by the VIP antagonist, but not by anti-IFN-alpha Ab, anti-IFN-gamma mAb, anti-IL-12 Ab, or anti-TGF-beta Ab. VIP did not inhibit IgE or IgG4 production in B cells or in B cells cultured with either T cells or monocytes. However, VIP inhibited IgE and IgG4 production when B cells were cultured with both T cells and monocytes.
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PMID:Vasoactive intestinal peptide differentially modulates human immunoglobulin production. 879 Jul 85

We have developed an automated robot that facilitates non-invasive isolation of a single cell with the most favorable properties from arrays containing >105 cells, thus allowing the establishment of new cell screening methods for bio-medicines. In this chapter, an outline of the proposed automated single-cell analysis and isolation system (hereafter called 'single-cell robot') is reviewed by comparison with a conventional fluorescence-activated cell sorter (FACS). The single-cell robot could perform high-throughput screening for both mammalian cells secreting the highest amount of bio-medicines (e.g. Chinese hamster ovary (CHO) cells or hybridomas), and stem cells with the highest pluripotency (e.g., embryonic stem (ES) cells), from huge number of cell libraries based on the recently proposed concept of "single cell-based breeding". The rational screening method for the de novo agonist design could also be performed using yeast cells expressing functional mammalian cytokine receptors (e.g., epidermal growth factor receptor (EGFR), somatostatin G protein-coupled receptor (SSTR5), and interleukin 5 receptor (IL5R)). Furthermore, the single-cell robot could comprehensively analyze the reaction between olfactory sensory neurons and specific odorants, which will shed light on how odorants are recognized by olfactory receptors. Taken together, these unique features of the proposed single-cell robot will contribute to the high-throughput development of forthcoming bio-medicines.
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PMID:Automated Single-Cell Analysis and Isolation System: A Paradigm Shift in Cell Screening Methods for Bio-medicines. 2994 92