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)

Mast cells of human skin, but not lung, adenoids, tonsils, or intestine, release histamine in response to substance P, vasoactive intestinal polypeptide, and somatostatin. The substance P receptor of skin mast cells is not of the NK-1, NK-2 or NK-3 subtypes of smooth muscle. Time course and calcium dependency of release by peptides differed from anti-IgE. With anti-IgE, the molar ratios of histamine:PGD2:LTC4 generated by skin mast cells was 1,000:25:2, whereas with substance P these ratios were 1,000:1:0.1. Similar results were obtained with the other neuropeptides. The ability of peptides to stimulate skin mast cell histamine release suggests a mechanism whereby their release from dermal nerve endings is coupled to changes in microvasculature.
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PMID:Interaction of neuropeptides with human mast cells. 246 22

1. Cells were dispersed from human foreskin using a mixture of collagenase and hyaluronidase and separated into mast cell-depleted (less than 1%) or enriched (greater than 75%) preparations by density-gradient centrifugation. 2. Challenge of gradient fractions with epsilon-chain-specific anti-human IgE stimulated the release of histamine, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The release of eicosanoids was significantly correlated with that of histamine, suggesting that they are derived from the mast cell population of the dispersate. In highly purified (76.2 +/- 4.2%) mast cell preparations, maximum net release of histamine, PGD2 and LTC4 was 3432 +/- 725, 84.9 +/- 10.8 and 6.6 +/- 1.2 pmol/10(6) nucleated cells. 3. The non-immunological stimuli substance P, vasoactive intestinal peptide (VIP), somatostatin, compound 48/80, morphine and poly-L-lysine released similar amounts of histamine to anti-IgE, but 12 to 21 fold less PGD2 and LTC4. 4. These studies suggest that IgE-dependent and non-immunological stimuli activate human skin mast cells by different secretory mechanisms, a hypothesis supported by our previous findings of differences in Ca2+ requirements and time-course of histamine release. Activation by the non-immunological mechanism may be of importance in vivo due to the close anatomical association between skin mast cells and dermal nerve-terminals containing neuropeptides.
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PMID:Differential release of histamine and eicosanoids from human skin mast cells activated by IgE-dependent and non-immunological stimuli. 247 53

Somatostatin (SOM) is a neuroendocrine tetradecapeptide that suppresses specific functions of differentiated T-cells and antibody-producing cells. The Jurkat line of human leukemic T-cells and U266 IgE-producing human myeloma cells bound [I-Tyr11]SOM specifically. The maximal level of specific binding was attained by 1-2 h at 22 degrees C for both types of cells and reversed by 70-85% within 2-3 h after the addition of excess nonradioactive SOM. Computer-assisted Scatchard analysis of the competition curves revealed two classes of binding sites for both cells. An average of 144 and 1295 high affinity receptors per Jurkat and U266 cells had a Kd value of 3 pM and 5 pM, respectively, whereas a large number of low affinity sites had Kd values of 66 nM and 100 nM. The affinity of the analogs somatostatin 28, [I-Tyr11]SOM, and [D-Trp8, D-Cys14]SOM for Jurkat and U266 cell lines, relative to SOM, suggested a degree of specificity similar to receptors on neuroendocrine cells.
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PMID:Distinct subsets of somatostatin receptors on cultured human lymphocytes. 256 57

When applied to the skin, phorbol esters (PEs) elicit signs of acute inflammation, suggesting they may induce the release of mediators from mast cells. Therefore, we have studied the effects of PEs on purified rat peritoneal and thoracic mast cells both alone and in conjunction with the calcium ionophore, A23187, and various other secretagogues that interact with immunoglobulin E (e.g., anti-IgE and Con A) or other cell surface receptors, e.g., somatostatin and compd 48/80. PEs alone caused little or no release of histamine. However, the PE 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 ng/ml) tremendously potentiated release induced by the calcium ionophore A23187, reducing the EC50 for A23187 from 832 ng/ml to 56 ng/ml. In the presence of suboptimal A23187 (50 ng/ml), only active tumor promoting PEs elicited histamine release. The EC50 values of the various active PEs were: TPA 5 ng/ml; 4 beta-PDD, 83 ng/ml; and 4-O-methyl-TPA, 807 ng/ml, with maximal histamine release ranging from 54 to 80%. TPA synergistically enhanced stimulation of histamine release by anti-IgE and Con A over the entire concentration-response range. In contrast, this synergism was absent when cells were stimulated with somatostatin and compd 48/80. Phorbol esters may act by increasing the activity of a calcium/phospholipid-dependent protein kinase (Ca/PL-PK). Mast cells do have Ca/PL-PK activity, and TPA in the presence of suboptimal A23187 induces protein phosphorylation comparable with other secretagogues. These results suggest that in the purified mast cell, PE-induced mediator release increases the sensitivity of release mechanisms for calcium, acts syngergistically with secretagogues interacting with IgE, and as suggested from structure-activity relationships, occurs via a specific mechanism of action perhaps involving the Ca/PL-PK.
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PMID:Characterization of the effects of phorbol esters on rat mast cell secretion. 257 54

This short review examines two examples of studies into the mechanisms of allergic responses which have particular relevance to inflammation research. The first is the ability of human skin mast cells, but not those derived from lung, adenoids, tonsils or intestine, to release histamine in response to stimulation by neuropeptides including substance P, vasoactive intestinal polypeptide (VIP) and somatostatin. The neuropeptide activation site does not appear to be a classical tachykinin receptor but rather a binding site of low affinity and low specificity capable of interacting with neuropeptides and compounds with similar physicochemical characteristics. In contrast to IgE-dependent activation, neuropeptide stimulation of skin mast cells induces a rapid release of histamine with minimal generation of PGD2 and LTC4. This pseudo-allergic reaction is thought to underlie the weal and flare response in the skin and may have a role in urticaria. The second example describes studies to elucidate the mechanisms of the late asthmatic response by use of a guinea-pig model. As in man, both early and late phase responses in the guinea-pig are inhibited by sodium cromoglycate whereas only the early response is inhibited by the beta-adrenoceptor stimulant drug salbutamol. Examination of bronchoalveolar fluid has shown a temporal relationship between an airways neutrophilia and the late response. However, pharmacological manipulation and the use of an anti-neutrophil serum has shown that these events are not interdependent. The role of the airways eosinophilia requires further investigation.
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PMID:Allergy or inflammation? From neuropeptide stimulation of human skin mast cells to studies on the mechanism of the late asthmatic response. 265 5

The functional and biochemical characterization of rat bone marrow derived mast cells (RBMMC) confirms both species-related differences between rat and mouse bone marrow-derived mast cells (MBMMC) as well as mast cell heterogeneity in a single species. Such RBMMC have the staining characteristics of mucosal mast cells and contain the mucosal mast cell protease. The RBMMC release the preformed granule mediator beta-hexosaminidase both in response to immunologic stimulation with 200 ng Ag (net release 15.8 +/- 3.8%) and in response to 1 microM calcium ionophore A23187 (net release 21.8 +/- 6.8%). However, compound 48/80, substance P, and somatostatin did not induce mast cell degranulation. In experiments with optimal beta-hexosaminidase release, the RBMMC generated similar quantities of the newly formed arachidonic acid metabolites leukotriene C4 and PGD2 when stimulated with either Ag or calcium ionophore A23187. The RBMMC incorporate [35S]sulfate into proteoglycans consisting of 90% chondroitin sulfates and 10% heparin. The chondroitin sulfates were comprised of chondroitin 4 sulfate and chondroitin sulfate diB sulfated disaccharides in a ratio of 4/1. Although we show that RBMMC and MBMMC share a low histamine content, functional IgE receptors and unresponsiveness to cromolyn and selective secretagogues (compound 48/80, substance P, and somatostatin), we also provide evidence that RBMMC differ from MBMMC in their profile of newly generated mediators, preformed granule proteoglycan, and lack of proliferative response to mouse IL-3.
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PMID:Functional and biochemical characterization of rat bone marrow derived mast cells. 297 57

Both cyclic and linear somatostatin-14 are potent histamine secretagogues in rat mast cell incubates. Linear somatostatin-14 is more effective than cyclic somatostatin-14 in a concentration range up to 10(-6) mol/l, in normal Sprague-Dawley rats, and even more responsive in sensitized hooded Lister rats. This additional mast cell stimulation capacity of linear somatostatin-14 depends on circulating IgE levels. No differences are observed in athymic rat mast cell incubates between the linear and the cyclic isomer of somatostatin-14. A direct unspecific interaction of linear somatostatin with cell surface antibodies can be concluded.
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PMID:Somatostatin-induced histamine release in mast cell incubates from thymusaplastic nude rats. 620 74

Incubation overnight of purified rat mast cells with glucocorticoids inhibited the release of histamine and [1-14C]arachidonic acid (and its metabolites) stimulated by three immunoglobulin (Ig) E-like secretagogues, anti-IgE, the antigen-ovalbumin and concanavalin A. In contrast, pretreatment with glucocorticoids did not affect either histamine or [1-14C]arachidonic acid release stimulated by somatostatin, compound 48/80 or the calcium ionophore A23187. Glucocorticoids inhibited IgE-like arachidonic acid and histamine release with an order of potency similar to their in vivo anti-inflammatory potencies (i.e., fluocinolone greater than dexamethasone greater than hydrocortisone greater than cortisone). This inhibition required several hours and was temperature-dependent, suggesting a specific glucocorticoid receptor mechanism. IgE-stimulated Ca++ influx was decreased by hydrocortisone pretreatment. These results suggest that glucocorticoids specifically uncouple IgE-mediated calcium flux with subsequent inhibition of histamine and arachidonic acid release.
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PMID:Inhibition of immunoglobulin, but not polypeptide base-stimulated release of histamine and arachidonic acid by anti-inflammatory steroids. 620 35

The release of mediators from unpurified human basophils challenged with anti-human myeloma IgE serum was suppressed significantly by somatostatin at respective concentrations of 3 x 10(-13) M to 10(-9) M for histamine and 10(-13) M to 10(-11) M for leukotriene D4, which had no effect on release elicited by ionophore A23187. A direct effect of picomole-nanomole concentrations of somatostatin on basophils predominated, as shown by the significant inhibition of immunologically stimulated mediator release from monocyte-free human basophils of 15 to 32% purity and from rat basophil leukemia cells. The dependence of basophil inhibition on the conformation of somatostatin was suggested by the lower potency of reduced and alkylated somatostatin and the lack of inhibitory activity of [D-Trp8] somatostatin. Somatostatin thus may mediate suppressive effects of sensory nerves in some basophil-dependent hypersensitivity reactions.
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PMID:Inhibition by somatostatin of the release of mediators from human basophils and rat leukemic basophils. 620 74

Previous studies in our laboratory have shown that substance P (SP), injected into benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) sensitized mice at the peak of the benzylpenicilloyl (BPO)-specific IgE response, suppressed these responses in isotype-specific fashion within 48 h. These studies also showed that SP, but not neurotensin (NT), serotonin (5-HT), somatostatin (SOM) or gastrin, suppressed BPO-specific memory IgE antibody-forming cell (AFC) responses induced in vitro, also in isotype-specific fashion. To investigate the mechanisms by which SP suppressed BPO-specific IgE AFC responses were induced in vitro, these responses were induced by culturing spleen cells from BPO-KLH sensitized mice for 5 days with BPO-KLH with or without whole SP, amino terminal SP (SP 1-4: Arg-Lys-Pro-Lys), or carboxy terminal SP (SP 8-11: Phe-Gly-Leu-Met). In some experiments, the SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP (D-SP) was included in culture. In other experiments anti-interferon monoclonal antibody (anti-IFN gamma mAb) was in culture. Whole SP and SP 8-11, but not SP 1-4, suppressed BPO-specific IgE AFC responses induced in vitro. The suppression obtained was IgE isotype-specific and dose-dependent. Inclusion of SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP inhibited suppression of BPO-specific memory IgE AFC responses by SP or SP 8-11. The SP-mediated suppression of BPO-specific memory IgE responses appeared to involve interferon gamma (IFN gamma).
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PMID:Neuropeptide-mediated regulation of hapten-specific IgE responses in mice. II. Mechanisms of substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vitro. 750 99


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