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)

In this experiment, the effects of different doses of vasoactive intestinal peptide (VIP) and naloxone (NLX) combinations on survival rates were investigated in rats exposed to 40% hemorrhage. A combination of 25 ng.kg-1 VIP+5 mg.kg-1 NLX showed the best results on survival. The important prospect of this combination is to have the most potent inhibitory effect on mast cell degranulation. When this combination was given together with shed blood reperfusion and 7.5% NaCl, survival rate increased relative to the administration of shed blood alone and of 7.5% NaCl. These findings suggest that inhibition of mast cell degranulation has a beneficial effect on severe hemorrhage.
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PMID:The effect of vasoactive intestinal peptide (VIP) and naloxone combination on survival rates in rats exposed to severe hemorrhage. 162 Jun 61

Several lines of evidence suggest a possible role for mast cell proteases in modulating the biologic effects of neuropeptides. To explore the potential of such interactions in human airway, we examined the activity of human tryptase, the major secretory protease of human lung mast cells, against several neuropeptides with proposed regulatory functions in human airway. Using highly purified tryptase obtained from extracts of human lung, we determined the sites and rats of hydrolysis of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), calcitonin gene-related peptide (CGRP), and the tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Tryptase hydrolyzes VIP rapidly at several sites (Arg12, Arg14, Lys20, and Lys21) with an overall kcat/Km of 1.5 x 10(5) M-1 s-1 and hydrolyzes PHM primarily at a single site (Lys20) with a kcat/Km of 1.9 x 10(4) M-1 s-1. Tryptase also rapidly hydrolyzes CGRP at two sites (Arg18 and Lys24) with a kcat/Km of 2.7 x 10(5) M-1 s-1. The tachykinins are not hydrolyzed by tryptase. These observations raise the possibility that tryptase-mediated degradation of the bronchodilators VIP and PHM combined with exaggerated mast cell release of tryptase may contribute to the increase in bronchial responsiveness and the decrease in immunoreactive VIP in airway nerves associated with asthma. The favorable rates of hydrolysis of CGRP suggest that tryptase may also terminate the effects of CGRP on bronchial and vascular smooth muscle tone and permeability.
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PMID:Degradation of airway neuropeptides by human lung tryptase. 169 72

Various stressful stimuli cause mast cell degranulation. Hemorrhagic shock is one such stressful stimulus which may cause mast cell degranulation and histamine release. Histamine may be involved in the pathophysiology of hemorrhage. It was reported that there are large amounts of histamine in the anterior and posterior lobes of the pituitary and the adjacent median eminence of the hypothalamus. Most of the histamine in the posterior pituitary is in mast cells. In addition, both vasoactive intestinal peptide (VIP) and histamine-containing neurons are available in the hypothalamus. It therefore seems reasonable to suppose that these three systems (i.e., mast cells, VIP-containing neurons, and histamine-containing neurons) may play an important role in the progression of hemorrhagic shock. 66 albino rats (200-250 g) of either sex were used. The presence of mast cells was examined by light microscopy. Hemorrhage caused mast cell degranulation in a correlation with the amount of blood loss. In all cases, the most intense degranulation was observed in the hypothalamus, especially the nucleus arcuatus, and in the subcutaneous tissue. The intensity of degranulation gradually decreased in the peripheral blood vessel, peritoneum and omentum, in this order. VIP prevented degranulation, but aprotinin and H1 and H2 receptor blockers did not.
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PMID:Mast cell degranulation in hemorrhagic shock in rats and the effects of vasoactive intestinal peptide, aprotinin and H1 and H2-receptor blockers on degranulation. 172 May 60

The peptides substance P (SP) and vasoactive intestinal peptide (VIP) released from peptidergic neurons have potent effects on gland secretion and on smooth muscle tone. Because mast cells release proteases during degranulation, and are located in many of the same tissue microenvironments into which SP and VIP are released, we wished to examine whether mast cell proteases, by cleaving and thus inactivating these peptides, could modulate their effects. We used active site-titrated preparations of the two major neutral proteases of mast cell granules, tryptase and chymase, to determine the sites and rates of cleavage of SP and VIP. The proteases were purified from dog mastocytomas. Tryptase cleaved VIP rapidly at two sites with a kcat/Km of 2.2 X 10(5) sec-1 M-1, but had no effect on SP. Chymase cleaved both SP and VIP at primarily a single site with kcat/Km of 3.9 X 10(4) and 5.4 X 10(4) sec-1 M-1, respectively. Thus, these data show that mast cell proteases degrade SP and VIP. The differences in peptidase activity between tryptase and chymase suggest that the consequences of protease release could vary according to mast cell protease phenotype and location in various tissues and species. Tryptase, by cleaving the bronchodilator VIP but not the bronchoconstrictor SP, might promote bronchial hyper-responsiveness in asthma by decreasing the nonadrenergic neural inhibitory influence mediated by VIP. In skin and other tissues, chymase might interrupt axon reflex-mediated neurogenic inflammation by cleaving SP.
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PMID:Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. 244 73

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

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

Recent evidence suggests that nonadrenergic airway relaxation may be controlled by vasoactive intestinal peptide (VIP). The magnitude and duration of smooth muscle relaxation in response to VIP may be influenced by rates of peptide degradation after release from efferent peptidergic neurons. To explore the potential role of mast cell mediators in modulating neural control of airway tone, we studied the effect of the mast cell proteases tryptase and chymase on airway smooth muscle relaxation induced by VIP in ferret airway. Tracheal rings precontracted by serotonin (10(-6) M) in a muscle bath were relaxed by VIP (10(-7) M). We found that protease-rich supernatant obtained by degranulation of dog mastocytoma cells reversed VIP-induced relaxation, as did highly purified tryptase and chymase incubated with the tracheal rings. Either enzyme completely reversed the effect of VIP, but tryptase was more potent than chymase, paralleling previous test tube observations on the relative rates of VIP cleavage by the two enzymes. Inhibitors of mast cell tryptase and chymase preincubated with the supernatant or with the purified proteases prevented reversal of VIP-induced relaxation. Mast cell proteases did not reverse the tracheal relaxation caused by the nonpeptide adrenergic agonist isoproterenol. These findings show that mast cell proteases tryptase and chymase counteract the smooth muscle relaxant effects of VIP in ferret trachea and suggest a potential role for the mast cell proteases in the modulation of nonadrenergic neural control of airway tone by VIP.
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PMID:Mast cell tryptase and chymase reverse airway smooth muscle relaxation induced by vasoactive intestinal peptide in the ferret. 249 55

The purpose of this study was to determine if asbestos-induced pulmonary fibrosis in the rat can affect the levels of autacoids and peptides in freshly isolated lung cells. Lung fibrosis was experimentally induced in rats by a single intratracheal instillation of 5 mg UICC Canadian chrysotile B fibers. Isolated lung cells were prepared from normal and from asbestos-exposed rats. These cells were also fractionated on bovine serum albumin (BSA) gradients. The contents of serotonin (5-HT), histamine (HIST), vasoactive intestinal peptide (VIP), and bombesin (BN) were measured in isolated total cell preparations as well as in density-fractionated cell populations from normal and from asbestos-exposed rats. Analysis of total lung cell preparation showed the presence of heterogeneous populations in normal rat lung. After asbestos exposure, there were significant changes in these cell populations as evidenced by significant increases in lymphocyte and mast cell numbers. In addition, increased levels of 5-HT, HIST, and VIP were observed in isolated lung cells obtained from rats exposed to asbestos 1, 3, and 6 months after instillation. BN content was unchanged 3 months after treatment, but was significantly increased at the 6 month-interval, suggesting a different pattern of response for this neuropeptide. Density fractionation of various cell populations further showed selective changes in specific cell fractions of lung after asbestos exposure. At 6 months, increased levels of 5-HT, HIST, and VIP were associated with cell fraction 7, whereas changes in BN content were found in cell fractions 2 and 3. Similarly, there was a significant increase of mast cells in fraction 7 at the 6-month interval.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in autacoid and neuropeptide contents of lung cells in asbestos-induced pulmonary fibrosis. 288 13

In addition to cholinergic neural mechanisms, airway tone is influenced by adrenergic mechanisms and by more recently described neural mechanisms which are non-adrenergic and non-cholinergic (NANC). Sympathetic innervation to human airways is very sparse and there is no functional adrenergic innervation of smooth muscle, although sympathetic fibres may supply ganglia, submucosal glands and bronchial vessels. Airway tone may be influenced by circulating adrenaline and there is some evidence that adrenaline secretion may be impaired in asthma. beta-Adrenoceptors (which are almost entirely of the beta 2-subtype) are localized to many cell types in airways and beta-agonist may be beneficial in airway obstruction, not only by directly relaxing airway smooth muscle (from trachea to terminal bronchioles), but by inhibiting mast cell mediator release, by modulating cholinergic nerves, by reducing bronchial oedema and by reversing the defect in mucociliary clearance. There is little evidence that beta-receptor function is impaired in asthma. Alpha-adrenoceptors, which are bronchoconstrictor, may be activated by inflammatory mediators and disease, and alpha-agonists cause bronchoconstriction in asthmatic patients. However, alpha-antagonists have little effect, which questions the role of alpha-receptors in asthma. NANC nerves which relax human airways have been demonstrated in vitro. Although the neurotransmitter is not certain, there is now convincing evidence that it may be vasoactive intestinal peptide (VIP) and a related peptide histidine methionine (PHM). VIP and PHM immuno-active nerves are found in human airways, and both peptides potently relay human airways in vitro (but not in vivo because of diffusion and metabolism problems).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adrenergic and non-adrenergic, non-cholinergic control of airways. 303 86

We have tested the effects of intravenous injections of substance P (SP), bradykinin (BK), somatostatin (SS) and vasoactive intestinal peptide (VIP) on the blood pressure, histaminemia and hematocrit in pentobarbital-anesthetized rats. The four peptides elicited a decrease of the mean arterial blood pressure which varied both in amplitude and in duration depending both on the peptide and on the doses utilized. The hypotensive effects of SP and VIP were more persistent than those caused by BK or SS. Only SP evoked an increase of histaminemia. Both SP and BK caused an increase of hematocrit. The change of hematocrit was more prominent and of longer duration after Sp than after BK. Pretreatment of rats with the antiinflammatory drug dexamethasone inhibited markedly the changes of blood pressure, histaminemia and hematocrit caused by SP. The hypotensive effects of BK, SS and VIP as well as the transient change of hematocrit evoked by BK were not affected by dexamethasone. The results suggest that part of the hypotensive activity and changes of hematocrit evoked by SP in rats is due to the release and action of histamine and possibly of other vasoactive substances, of mast cell origin. The results also indicate that mast cell mediators, particularly histamine, are unlikely to be instrumental in the hypotensive activity of BK, SS or VIP in rats.
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PMID:Evaluation of the contribution of mast cell mediators to the hypotensive activity of various peptides in rats. 619 Dec 39


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