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)

Staphylococcal enterotoxin B (SEB) was tested in rodent mast cell cultures for the release of serotonin. Both rat RBL-2H3 mast cells and murine peritoneal cells released serotonin after SEB stimulation in culture. Release of serotonin in RBL-2H3 cells depended on the concentration of SEB; an appreciable release was seen at 50 micrograms/ml. The release of serotonin was not due to cell death. Serotonin release could be enhanced by bradykinin but not by vasoactive intestinal peptide, substance P, lipopolysaccharide from Salmonella typhimurium, the calcium ionophore A23187, acetylcholine, adenosine, 5-hydroxyeicosatetraenoic acid, indomethacin, or phorbol myristate acetate. SEB bound directly to the membrane of RBL-2H3 mast cells, and the SEB-binding site, the presumptive receptor, appeared to be a protein. The SEB receptor could not be capped under membrane-capping conditions, and serotonin release could not be enhanced by attempts to cross-link the receptor. These results suggest that mast cells may be an important cell type involved in SEB toxicosis and that release of serotonin may be enhanced by activation of the kinin-kallikrein system.
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PMID:Effects of staphylococcal enterotoxin B on rodent mast cells. 137 85

Excessive fluid and electrolyte secretion, resulting symptomatically in diarrhea, has been associated with mast cell activation in a variety of experimental and clinical settings. The present study has used a human colonic epithelial cell line to examine mechanisms underlying this phenomenon. Acute addition of mixed mast cell mediators (as a lysate of rat basophilic leukemia cells) to epithelial cells led to prompt and sustained chloride secretion. The response was partially inhibitable by an antihistaminic drug and an adenosine antagonist, suggesting that histamine, adenosine, and possibly other mediators are responsible for producing the acute effect. Supernatants from immunologically activated rat basophilic leukemia cells had similar effects. Chronic exposure of epithelial cells to the lysate mediator preparation, followed by washing, had no effect on their basal electrical or electrolyte-transporting properties. However, the chloride secretory response of the cells to subsequent addition of vasoactive intestinal peptide, carbachol, and heat-stable enterotoxin of Escherichia coli was significantly enhanced, whereas responses to an adenosine agonist or PGE1 were unaffected. This study has, therefore, demonstrated two ways in which mast cell mediators can directly influence intestinal epithelial cells to secrete more chloride and, hence, to enhance fluid secretion in the gut. The findings may be of relevance to our understanding of inflammatory diarrhea and may aid the development of novel therapies for this disorder.
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PMID:Immune-related intestinal chloride secretion. III. Acute and chronic effects of mast cell mediators on chloride secretion by a human colonic epithelial cell line. 165 Mar 88

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

We have examined cells dispersed enzymatically from three different sites in the bovine lung (tracheal mucosa, bronchial mucosa and parenchyma) and the skin, in order to ascertain whether the bovine model could be used to study mast cell heterogeneity. Histochemically there were two sub-populations of mast cells present in both lung and skin (on the basis of toluidine blue staining and the sensitivity to formalin fixation), but their proportions were similar in all sites studied. Skin mast cells contained approximately twice the amount of histamine than their counterparts in the lung (P less than 0.05). Functional heterogeneity was examined by in vitro release of histamine following secretagogue challenge. Calcium ionophore induced a substantial release of histamine; skin mast cells releasing significantly more histamine than any of the lung mast cells (at 10 microM ionophore, 37.1% and 20.7% net histamine release, respectively, P less than 0.05), although the time-course of release from the two tissues was similar. The neuropeptides vasoactive intestinal peptide and somatostatin induced a modest but statistically significant release of histamine from both skin and lung mast cells, whilst substance P only induced histamine secretion from skin mast cells. A range of other potential immunological and non-immunological secretagogues was unsuccessful in eliciting histamine release from mast cells in any of the tissues. We conclude that there were no convincing histochemical differences between mast cells from the sites examined in the lung or skin. Additionally, there was no discernable functional heterogeneity between mast cells within the lung, but functional differences were evident between mast cells of the bovine lung and skin. However, in the absence of a suitable immunological stimulus the bovine model cannot be regarded as a good model of mast cell heterogeneity.
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PMID:Structural and secretory characteristics of bovine lung and skin mast cells: evidence for the existence of heterogeneity. 171 May 30

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 nasal mucosa is innervated by the sensory, parasympathetic, and sympathetic nervous systems. Nociceptive sensory nerves are stimulated by mucosal injury, inhalation of irritants, or mast cell degranulation and release of the calcitonin gene-related peptide, the tachykinins substance P and neurokinin A, and other peptides by the axon response mechanism. Sensory nerve stimulation initiates systemic reflexes, such as the sneeze, and central parasympathetic reflexes which release acetylcholine, vasoactive intestinal peptide, and other peptides and lead to glandular secretion. In concert, these proinflammatory neural responses lead to vasodilation, vascular permeability, and glandular secretion. Sympathetic nerves release neuropeptide Y and norepinephrine, potent vasoconstrictors which act to decompress the nasal mucosa and produce nasal patency. The balance between the effects of parasympathetic and sympathetic neurotransmitters may regulate nasal homeostasis, whereas the nociceptive sensory system may be held in reserve as a defense mechanism. Dysfunction of these systems may lead to pathological nasal syndromes. In the future, specific neuropeptide agonists and antagonists may be useful for the treatment of human rhinitic diseases.
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PMID:Neuropeptides and nasal secretion. 192 55

Recent research has disclosed that neurotransmitters and neuropeptides released within the autonomic nervous system exert homeostatic control of nasal secretion. Although cholinergic and adrenergic influences have long been thought to be the predominant mechanisms, the nonadrenergic, noncholinergic responses may have more suitable, longer-lasting effects. Peptides from sensory nerves, such as calcitonin gene related peptide, substance P, and neurokinin A, may participate in axon response-mediated vasodilation and plasma extravasation. Substance P and gastrin releasing peptide may induce glandular secretion. Defensive responses to local mucosal injury may be amplified by axon response, which initiates these vascular and glandular reactions. Cholinergic effects are primarily responsible for mediating parasympathetic reflexes, but vasoactive intestinal peptide may regulate acetylcholine release, augment glandular secretory responses, and have a vasodilatory effect. In the sympathetic nervous system, neuropeptide Y probably functions as a long-acting vasoconstrictor. Integration of sympathetic and parasympathetic influence may regulate the normal nasal cycle, and sensory and parasympathetic defensive reflexes may respond to epithelial and mast cell stimulation. It is possible, then, that the pathophysiology of vasomotor rhinitis involves an exaggeration of these neural influences.
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PMID:Neuropeptides and nasal secretion. 222 24

Our studies have clearly shown that neuropeptides have a profound effect on immunoglobulin synthesis both in vivo and in vitro. The effects varied according to the neuropeptide added or the tissue from which the lymphocytes were obtained. Substance P caused the most pronounced enhancement of both functions, especially in Peyer's patch cells, where it selectively increased IgA synthesis. Somatostatin was inhibitory, and the effect of vasoactive intestinal peptide varied according to the source of the cells. We have previously shown that neuropeptides also cause mast cell secretion and that only substance P was effective in this regard on intestinal mucosal mast cells. Therefore, we looked for microanatomic relationships between peptidergic nerves and immune effector cells. Mast cells appear to have structural associations with neuropeptides-containing nerves in the intestine. Nerve growth factor, known to promote the growth of sensory afferent and sympathetic nerves, has significant direct effects on mast cells. In vitro, this substance caused enhanced antigen mediated histamine release and, in vivo, extensive mast cell hyperplasia. Also, in humans, we were able to produce increased numbers of mast cell/basophil colonies from peripheral blood in the presence of nerve growth factor.
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PMID:Neuropeptides and immunity. 244 42

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


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