Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine release from isolated mast cells stimulated with somatostatin resembled that induced by other basic agents. The process was rapid, independent of added calcium or phospholipids, non-cytotoxic, species and tissue specific, not mediated through cell-fixed antibodies or glucoreceptors, and inhibited by antagonists of the polyamine receptor. Somatostatin and other polycations may then act through a common receptor or binding site on the mast cell membrane.
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PMID:Histamine secretion from mast cells stimulated with somatostatin. 245 92

1. Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration-related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 microM to 30 microM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP), neurotensin, bradykinin and Lys-bradykinin induced negligible histamine release. 2. The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK-1, NK-2 or NK-3 receptors described in smooth muscle. 3. The relative potencies of substance P and its fragments SP2-11, SP3-11, SP4-11 and SP1-4 in releasing histamine from human skin mast cells suggests that both the basic N-terminal amino acids and the lipophilic C-terminal portion of substance P are essential for activity. 4. Peptide-induced histamine release, like that induced by compound 48/80, morphine and poly-L-lysine, is rapid, reaching completion in 10-20 s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. 5. The substance P analogue, [D-Pro4,D-Trp7,9,10] SP4-11 (SPA), not only reduced substance P-induced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE. 6. The similar characteristics of histamine release induced by substance P, VIP, somatostatin, compound 48/80, poly-L-lysine and morphine suggest that they share a common pathway of activation-secretion coupling distinct from that of IgE-dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non-immunological stimuli including neuropeptides may reflect a specialised function for these cells.
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PMID:Characterization of neuropeptide-induced histamine release from human dispersed skin mast cells. 246 82

To study the nature and extent of mast cell heterogeneity within a single species, we have developed methodologies to isolate rat lung mast cells (LMC) and have compared these to peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC). In normal and athymic nude (rnu/rnu) rats, a single intratracheal administration of bleomycin (5 U/kg) leads to pulmonary fibrosis accompanied by parenchymal hyperplasia of mast cells that are histochemically like PMC rather than IMMC. Using collagenase digestion of fibrotic rat lungs (30-80 days after bleomycin treatment), we recovered an average of 58.1 x 10(6) viable cells per rat, containing 2.5% mast cells. Control experiments in which PMC were subjected to the isolation procedure used for LMC showed that there was no qualitative effect on PMC, but that a reduction of 26-60% in responsiveness to secretagogues occurred. Isolated LMC secreted histamine in response to 48/80, A23187, substance P, VIP and somatostatin and bradykinin, but at lower levels than PMC. The anti-allergic compound theophylline, which does not inhibit antigen-induced histamine secretion by IMMC, was effective against both LMC and PMC. Taken together, the thymus independence of pulmonary mast cell hyperplasia, the histochemical characteristics and the responsiveness to secretagogues and anti-allergic compounds indicate that the majority of dispersed LMC are similar to PMC rather than to IMMC. Whether LMC should be considered analogous to PMC or, because of their size, histamine content and responsiveness to many secretagogues, intermediate between PMC and IMMC, remains to be determined through additional studies.
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PMID:Isolation and characterization of lung mast cells from rats with bleomycin-induced pulmonary fibrosis. 246 79

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

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

Somatostatin prevents hemorrhagic gastric erosions produced by ethanol. In this paper we describe studies with linear (reduced) and cyclic (oxidized) synthetic somatostatin-14 in the rat model of ethanol-induced gastric mucosal injury. The linear form of somatostatin was more potent at concentrations of 10(-9) to 10(-8) mol per rat than the cyclic isomere. However, at a concentration of 10(-7) mol per rat i.p. injection of linear somatostatin significantly (P less than 0.01) enhanced gastric erosions caused by the alcohol. The area of hemorrhagic mucosal lesions correlated significantly (r = -0.846) with mast cell depletion in the gastric mucosa of the animals. Increased vascular permeability and mast cell degranulation were also observed after intradermal injection of linear or cyclic somatostatin. The 'cytoprotective' as well as the aggravating potency of linear somatostatin may be connected to gastric mucosal mast cell activity in the rat.
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PMID:Dose-dependent effects of linear and cyclic somatostatin on ethanol-induced gastric erosions: the role of mast cells and increased vascular permeability in the rat. 287 90

Somatostatin (S) inhibits hemorrhagic gastric erosions produced by ethanol. In this study we compared the dose-dependent effects of linear (reduced) and cyclic (oxidized) S with respect to mast cell degranulation. The gastric mucosal injuries were more inhibited by linear S than by cyclic S. But linear S aggravated injury at a certain dose (10(-7) mol/rat). Mucosal mast cell degranulation correlated significantly with the area of hemorrhagic mucosal lesions (r = 0.91). Both cytoprotection as well as aggravation potency of S may be connected to gastric mucosal mast cell activity in the rat.
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PMID:Effects of somatostatin on ethanol-induced gastric erosions in the rat: role of mast cells. 287 24

Studies on the morphological distribution of histamine (HA)-secreting neurons and their hypothalamic projections suggest that HA may play a key role in regulating neuroendocrine functions, some of which have been recently elucidated. To investigate possible interactions between the somatotropinergic and histaminergic systems in the brain, the effects of GRF-44 [0.1-10 micrograms intracerebroventricular (icv)] and somatostatin (SS-14; 0.1-10 micrograms, icv) on HA in five different parts of the hypothalamo-hypophyseal system, and in the hippocampus and frontal cortex, were studied using a highly sensitive HPLC system for determination of HA. GRF-44 (1 microgram, icv) elicited significant (P less than 0.005) increases in the concentration of HA in the anterior hypothalamus, posterior hypothalamus, median eminence, adenohypophysis, neurohypophysis, frontal cortex, and, to a lesser extent, in the hippocampus, after a clear time-dependent pattern with maxima 15 min after injection. In contrast, SS-14 (1 microgram, icv) significantly (P less than 0.005) decreased the levels of HA in all areas studied, except in the neurohypophysis. The SS-induced HA levels reached minima 30 min after injection. The antagonistic effects of GRF-44 and SS-14 on the release of brain HA were dose dependent, showing an inverse linear correlation within the range 0.1-10 micrograms in the anterior hypothalamus (r = -0.59) and posterior hypothalamus (r = -0.75). Responses of HA to GRF-44 and SS-14 (range: 0.1-10 micrograms) also exhibited an inverse linear correlation in the median eminence (r = -0.90) and adenohypophysis (r = -0.58), while in the hippocampus and frontal cortex the antagonistic effects of GRF and SS displayed an inverse curvilinear correlation. SS-14 ED50 values ranged from 0.6 to 1.75 nmol with Emax of 0.65-6.10 nmol. GRF-44 ED50 values ranged from 0.02-0.3 nmol and the Emax values oscillated between 0.2 and 1.90 nmol in the regions studied. The greatest responses of HA to GRF-44 and SS-14 were obtained in the hypothalamo-hypophyseal system. Although brain HA is present in both the neuronal and the mast cell compartments, changes induced in the concentration of HA by centrally administered GRF-44 and SS-14 appear to occur mostly in the neuronal compartment. Therefore, it is likely that the somatotropinergic and histaminergic systems reciprocally interact at the central level to regulate still unknown neuroendocrine functions.
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PMID:Antagonistic effects of growth hormone-releasing factor and somatostatin on brain histamine. 289 95

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


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