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)

Inflammatory or allergic conditions, as well as situations where healing and repair processes occur, are characterized by the presence of increased numbers of mast cells. Previous work on the effect of neuropeptides on mast cell mediator release showed that only substance P caused such release from intestinal mucosal mast cells [Shanahan, F., Denburg, J. A., Fox, J., Bienenstock, J. & Befus, A. D. (1985) J. Immunol. 135, 1331-1337]. Accordingly, we investigated the microanatomical relationship between mast cells and enteric nerves in normal rat intestine and parasite-infected rat intestine, in which mucosal mast cell hyperplasia occurs. Combined immunohistochemistry for neuron-specific enolase and staining with alcian blue at pH 0.5 was employed on paraffin-embedded sections of normal and Nippostrongylus brasiliensis-infected rat jejunum. Sixty-seven percent of intestinal mucosal mast cells were touching subepithelial nerves, and an additional 20% were within 2 micron of nerves. Assessment of the proportion of the lamina propria occupied by mast cells (12.5%), the average mast cell area (121 +/- 28 microns 2), and the density of enteric nerves (one per 788 +/- 151 microns 2) suggested that the association was 5 times greater than would be expected by chance alone (P less than 0.0001). In consecutive sections, the nerves in contact with mast cells were also shown to contain substance P and/or calcitonin-gene-related peptide. Electron microscopy confirmed this association: 8% of the mast cells in infected rats exhibited membrane-membrane contact with unmyelinated axons containing 70- to 170-nm dense-core vesicles, and an additional 31% were situated less than 250 nm from nerves. Other mast cells appeared to embrace nerve bundles through the projection of lamellopodia. These data provide systematic quantitative evidence that a structural foundation for communication between the immune and nervous systems exists in the rat gastrointestinal tract.
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PMID:Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. 243 89

The 37-amino-acid calcitonin gene-related peptide (CGRP) occurs as a result of alternative processing of mRNA from the calcitonin gene. The potency of CGRP as a vasodilator and the occurrence of the peptide in nerves associated with blood vessels suggest an important role for CGRP in the regulation of blood flow. The finding that CGRP induces protracted vasodilatation when administered extra-vascularly, to mimic release from nerves, has led us to investigate how the vasodilator activity of CGRP is controlled in vivo. CGRP is often co-localized with substance P in C-fibre nerves. Here, we demonstrate that injection of CGRP with substance P into human skin converts the long-lasting vasodilatation induced by CGRP into a transient response. Experiments in animals reveal that the phenomenon is dependent on the action of proteases from mast cells stimulated by substance P. The results reveal a new regulatory interaction between two neuropeptides and provide evidence for an in vivo role for mast cell proteases.
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PMID:Substance P regulates the vasodilator activity of calcitonin gene-related peptide. 245 10

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. The mechanisms involved in tachykinin-induced oedema were investigated in rat skin and interactions between the tachykinins and calcitonin gene-related peptide (CGRP) were studied. 2. Intradermal injections of the tachykinins, substance P, neurokinin A and neurokinin B, stimulated local oedema formation which was in each case potentiated by co-injection of the vasodilator CGRP. Oedema induced by substance P, in the presence and absence of CGRP, was significantly inhibited by pretreatment of rats with a combination of the histamine H1 antagonist, mepyramine, and the 5-hydroxytryptamine antagonist, methysergide. Oedema induced by neurokinin A or B was not inhibited by this pretreatment. 3. Intradermally-injected CGRP induced a long lasting increase in local blood flow, which was measured with a laser Doppler blood flow meter. The simultaneous injection of substance P, but not of the structurally-related neurokinins, caused a loss of the prolonged vasodilator activity of CGRP. 4. These results show that oedema induced by substance P is partially dependent on mast cell amines and that only substance P causes a loss of the prolonged vasodilator activity of CGRP. 5. We suggest that the ability of substance P to prevent the persistent vasodilator activity of CGRP may be a direct consequence of substance P-induced activation of mast cells.
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PMID:Interactions between the tachykinins and calcitonin gene-related peptide lead to the modulation of oedema formation and blood flow in rat skin. 247 Apr 60

The purpose of the study was to compare the secretory activity of thyroid and parathyroid mast cell populations during a rise of the level of calcium regulating hormones in the body. 65 rats were divided into 5 equal groups. The animals were given single intraperitoneal injections of the following agents: the 1st group--parathyroid hormone, 5 units per 100 g of body mass; the 2nd group--trilon B, 0.5 ml of 5% solution; the 3rd group--calcitonin, 1.5 units per 100 g of body mass; the 4th group--calcium gluconate, 0.7 ml of 10% solution; the 5th group--distilled water, 0.7 ml; after that the animals were killed with a 12 min. interval. The index of mast cell degranulation was calculated in the thyroid and parathyroid. The administration of PTH and trilon B caused a significant increase in parathyroid mast cell degranulation 36-120 min. after injection whereas secretory activity of thyroid tissue basophils did not change. Mast cell populations of both glands reacted in a similar way to the administration of calcitonin and calcium gluconate expressed in significant enhancement of degranulation 24-84 min. after injection. The results obtained indicated an important role of thyroid and parathyroid tissue basophils in the implementation of inter- and intraorganic regulatory interactions.
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PMID:[Effect of calcium-regulating hormones on the secretory activity of basophils of the thyroid and parathyroid glands]. 312 11

A quantitative mouse calvarial bone resorption assay was employed to investigate the effects of the mast cell products, heparin and histamine, and of salmon calcitonin. 'Amorphous' heparin, containing a range of molecular weight fractions, inhibited resorption by 15-20% at concentrations of 0.75-5.0 mg/ml. A 'defined' heparin species of mol.wt 13 500 inhibited resorption by 14-28% at 10(-5)-10(-4) mol/l. Histamine inhibited resorption by 19-55% at 10(-3)-10(-2) mol/l. It is proposed that heparin and histamine depress coupled bone resorption and formation and may lead to net loss of bone. Salmon calcitonin inhibited resorption at concentrations as low as 10 pg/ml. 'Amorphous' (but not 'defined') heparin blunted calcitonin induced inhibition of bone resorption and may derepress osteoclasts.
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PMID:Effects of heparin, histamine, and salmon calcitonin on mouse calvarial bone resorption. 371 18

Mastocytosis gives rise to clinical symptoms such as flushing, itching and diarrhoea. We report a patient with urticaria pigmentosa without evidence of systemic involvement but with recurrent episodes of diarrhoea. The patient had elevated circulating levels of calcitonin, which might have been a mediator of her diarrhoea. We suggest that serum calcitonin level should be checked in patients with mast cell disease and diarrhoea.
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PMID:Hypercalcitoninaemia in a patient with urticaria pigmentosa. A possible cause of diarrhoea. 673 Oct 41

Substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) coexist in nerve fibres in the skin. CGRP causes erythema upon intracutaneous injection. The erythema is independent of axon reflexes and release of mast cell histamine. SP is known to produce a flare reaction that is dependent on axon reflexes and release of mast cell histamine. The flare reaction to NKA is known to depend predominantly on axon reflexes. The purpose of the present study was to investigate possible cooperation between SP and CGRP. SP was found to shorten the duration of the reddening induced by CGRP, injected concomitantly. NKA did not shorten the duration of the CGRP response. Local elimination of mast cells in the skin by treatment with compound 48/80 had the effect that SP lost its ability to shorten CGRP-evoked erythema. These observations support the suggestion that an SP-evoked release of proteolytic enzymes from mast cells could lead to accelerated degradation of CGRP.
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PMID:Interaction between tachykinins and CGRP in human skin. 750 67

Rabbit leptomeningeal arteries contain granular cells resembling mast cells that frequently contact autonomic and sensory nerve profiles. In the present in vitro study, we determined whether these cells could be stimulated by substance P (SP) and calcitonin gene-related peptide (CGRP), which are stored and released by sensory C fibers. Immunohistochemistry of the middle cerebral artery showed that 5-HT was stored only in mast cell-like granules. This pool of 5-HT decreased in a dose-dependent manner when exogenous SP and CGRP were added to the incubation solution or when endogenous neuropeptides were released from nerve terminals by capsaicin. The simultaneous administration of CGRP and SP induced a dramatic exocytosis and a 5-HT release significantly greater than the sum of the individual effects of the two neuropeptides. We conclude that, as in classical connective tissue mast cells, the amine content of these granular cells can be released by a degranulation process induced by neuropeptides. The effects of capsaicin suggest that this phenomenon can be triggered by axon reflex of C fibers. The data also provide the first evidence of a synergistic action of SP and CGRP on mast cell degranulation.
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PMID:Substance P, calcitonin gene-related peptide, and capsaicin release serotonin from cerebrovascular mast cells. 752 17

The study describes the distribution of mast cells and of substance P (SP) and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the rat palatal mucosa, focusing on the anatomic relationship between these tissue elements. The maxilla of 10-14-wk-old rats was dissected free, fixed, demineralized and frozen. Consecutive sections were stained with avidin peroxidase or processed for immunohistochemistry. In order to define the correlation between nerve fibers and mast cells, double staining techniques were used. The distance between each avidin-positive mast cell and the nearest detectable nerve fiber was determined. 5-Hydroxytryptamine- (5-HT) and avidin peroxidase-positive mast cells were frequently seen in the palatal mucosa but were rarely found in the gingival area. A large number of nerve fibers showing SP- and CGRP-like immunoreactivity were seen, particularly in association with blood vessels. Some nerve fibers were located in contact with or very close to the mast cells but the vast majority of mast cells showed no close anatomic association to nerve fibers. The nerve fibers and mast cells were mainly concentrated to the same regions in the palatal mucosa where blood vessels occurred. The observations suggest that in the rat palatal mucosa the main functional relationship relates to SP/CGRP and the blood vessels, and only to a minor degree to SP/CGRP and mast cells.
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PMID:Anatomic relationship between substance P- and CGRP-immunoreactive nerve fibers and mast cells in the palatal mucosa of the rat. 753 32


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