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)

The possibility that VIP (Vasoactive intestinal peptide) could influence the enterochromaffin (EC) cell secretion of serotonin (5HT) and the action of VIP on the mast cell population of lamina propria were investigated in Wistar rat colon infused with a short chain fatty acid solution (sodium acetate), during a 1 h period. Under the action of an intravenous injection of synthetic porcine VIP, 14 micrograms/kg/h), the number of EC cells diminished significantly in the cecum and left colon, when compared to non-injected animals, both infused with a sodium acetate solution. At the same time, the number of mucosal mast cells in the crypts and lamina propria decreased significantly in the cecum. The postulate we put forward is that these VIP-induced changes are exerted through the stimulation of 5HT released from EC cells not only under normal physiological conditions but probably also under pathological conditions.
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PMID:Influence of VIP on the number of enterochromaffin and mucosal mast cells in the colon of the rat. 143 71

1. Systemic capsaicin treatment of the pig depletes the content of sensory neuropeptides (CGRP and tachykinins) in the airways mucosa and skin, without affecting sympathetic and parasympathetic nerves containing NPY and VIP, or the presence and appearance of inflammatory cells including mast cells. Acute capsaicin exposure caused release of sensory neuropeptides and catecholamines, and marked vasodilation in the airways and skin, without signs of plasma protein extravasation or bronchoconstriction. Capsaicin pretreatment effectively desensitizes against local challenges with capsaicin in the airways and skin, as revealed by the absence of vasodilatory responses 2 days later. 2. Cigarette smoke exposure induces marked vasodilatation, lasting for about 5 min in both the upper and lower airways, which seems not to be primarily caused by particulate matter or nicotine in the smoke. Except for a minor capsaicin-sensitive component in the nasal circulation, these responses probably do not involve neural activation, mast cell degranulation or prostaglandin formation. Rather, it is concluded that vapour phase components act on the vessels via unknown mechanisms. 3. Sensitization of pigs with s.c. injections of ascaris antigen was successful, resulting in typical wheal and flare reactions in the skin and bronchoconstriction after local challenge with antigen. The reactivity to ascaris is probably mediated by antibodies of the IgE isotype. 4. Histamine-containing mast cells and sensory neuropeptide-containing nerve fibers show close morphological association around blood vessels in the pig skin. Both alcian blue-positive mast cells and capsaicin-sensitive sensory nerves are present close to the pig airways epithelium. Sensory neuropeptide-containing nerves are also abundant around airways mucosal blood vessels, whereas the bronchial smooth muscle is sparsely innervated. 5. Allergen and histamine injections in the skin caused similar responses consisting of flare and protein extravasation. Allergen challenge in the airways induces marked vasodilatation lasting for 60-90 min in the pig bronchial and nasal circulations. Histamine seems to be important in the early phase (0-20 min) of these responses in the airways, while cyclooxygenase products (possibly PGD2) may be responsible for the longlasting component. A cyclo-oxygenase product is presumably also released from the lung into the circulation after bronchial allergen challenge and thereby induces a delayed, long-lasting nasal vasodilatation. Histamine may be the main bronchoconstrictor agent released in the immediate allergic reaction of the pig. 6. The flare, but not the protein extravasation reaction, to allergen and histamine injections in the skin, was inhibited by capsaicin pretreatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Airways vasodilatation in the immediate allergic reaction. Involvement of inflammatory mediators and sensory nerves. 203 38

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

Cultured human myeloma cells of the U266 line and leukemic T cells of the Jurkat line bound synthetic [125I]Tyr10-vasoactive intestinal peptide1-28 ([125I]VIP1-28) specifically and with an affinity similar to that of neuroendocrine cells. Specific binding reached equilibrium after 2 h at 22 degrees C for both myeloma cells and T cells, attained a maximum of 57 to 71% of total binding, and was reversed in 1.5 to 3 h by an excess of non-radioactive VIP1-28. Analyses of the ligand concentration-dependence of binding of the ligand concentration-dependence of binding of [125I]VIP1-28 revealed a mean Kd of 7.6 nM for a mean of 41,207 receptors per myeloma cell and 5.2 nM for 12,266 receptors per T cell. The relative affinity of binding of mast cell-derived VIP10-28 free acid and synthetic analogues suggested differences in specificity between lymphocyte and neuroendocrine receptors. Distinct sets of receptors thus appear to mediate the effects of VIP on functions of both antibody-producing cells and T cells.
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PMID:High-affinity receptors for vasoactive intestinal peptide on human myeloma cells. 253 66

Radioimmunoassays for neuroendocrine vasoactive intestinal peptide (VIP1-28) detected 30-120 fmol of structurally related peptides in extracts of 10(7) mouse peritoneal mast cells, bone marrow-derived mast cells, cultured PT-18 and C1.MC/C57.1 lines of mast cells, and rat basophilic leukemia (RBL) cells. No VIP was found in peritoneal cells of mast cell-deficient WBB6F1-W/Wv mice, whereas the amounts extracted from peritoneal cells of the congenic normal (WBB6F1-+/+) mice were similar to those from cultured mouse mast cells. Sephadex G-25 gel filtration resolved two different-sized variants of VIP from mouse mast cells and RBL cells. Amino acid sequence analyses showed that the smaller variant is VIP10-28. The principal amino-terminally larger variant of VIP from C1.MC/C57.1 mouse mast cells and RBL cells exhibited amino acid sequence homology with VIP(-6)-28, and this sequence was established for the corresponding larger VIP from PT-18 mast cells. Polymerase chain reaction amplification of two different substituent sequences of prepro VIP in RBL cell RNA identified the VIP message. VIP10-28 was released from mouse mast cells concurrently with histamine by IgE-dependent stimulation. Rodent mast cell-derived VIP thus consists of both the truncated VIP10-28 and amino-terminally larger forms that appear to be generated by peptidolysis of a preproVIP similar to that found in neural cells.
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PMID:Variants of vasoactive intestinal peptide in mouse mast cells and rat basophilic leukemia cells. 840 43

The effect of VIP on mast cell invasion/degranulation in testicular interstitium of stressed (immobilization and cold) and beta-endorphin-treated rats were investigated. Fifty-three Wistar male rats were used in four series of experiments. Initially, the effect of immobilization and cold stress on mast cell invasion and degranulation in testicular interstitium was examined in three age group of rats: 15 (n = 6), 30 (n = 6), and 45 (n = 7) days of age. Five animals per age group were used as controls. Because the most obvious effect of the stress on mast cell invasion/degranulation in testicular interstitium was observed in 45-day-old rats, the action of VIP in stressed and beta-endorphin-treated rats was only investigated at this age group. Mast cells and Leydig cells were evaluated by using histochemical and light microscopic protocols. Stress caused mast cell accumulation and degranulation in the testicular interstitium. Stress decreased heparin synthesis and possibly increased histamine content of mast cells. The effect of beta-endorphin was not as high as seen with stress. In some areas of testicular interstitium of stressed rats, there were aplasic and/or inactive Leydig cells. VIP inhibited proliferation and degranulation of mast cells, increased heparin content of the cells, and protected Leydig cells. By way of mast cell accumulation and degranulation in the testicular interstitium, exposure to stress may lead to Leydig cell damage and infertility. VIP may be involved in the protection of normal testicular function under stress conditions.
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PMID:The effect of vasoactive intestinal peptide (VIP) on mast cell invasion/degranulation in testicular interstitium of immobilized + cold stressed and beta-endorphin-treated rats. 884 72

The pathogenesis of cold-restraint stress ulcer involves various factors and is not completely understood. Mast cell degranulation, increased gastric muscular contractility, diminished mucosal blood flow, release of several biogenic amines, activated polymorphonuclear leukocytes, and lipid peroxidation which results from toxic oxygen molecules were suggested to be related to the production of gastric damage by cold-restraint stress. Recent evidence strongly indicates that VIP has a modulatory effect on tissue injury. Sprague-Dawley rats were used in two series of experiments. One set of rats was exposed to cold-restraint stress with some of the rats pretreated with VIP. The second set of rats was exposed to cold-restraint stress and then was administered VIP for different durations. Cold-restraint stress induced gastric lesions and mast cell degranulation and also increased lipid peroxidation in gastric tissue. VIP prevented stress-induced ulcers and mast cell degranulation and protected gastric tissue from lipid peroxidation. When VIP was used after induction of stress ulcer it was therapeutically beneficial. Thanks to its antioxidant and anti-inflammatory activity, VIP can be valuable in the prevention of gastric mucosal damage induced by cold-restraint stress.
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PMID:The protective effect of vasoactive intestinal peptide (VIP) on stress-induced gastric ulceration in rats. 992 25

Mast cells that are in close proximity to autonomic and enteric nerves release several mediators that cause neuronal hyperexcitability. This study examined whether mast cell tryptase evokes acute and long-term hyperexcitability in submucosal neurons from the guinea-pig ileum by activating proteinase-activated receptor 2 (PAR2) on these neurons. We detected the expression of PAR2 in the submucosal plexus using RT-PCR. Most submucosal neurons displayed PAR2 immunoreactivity, including those colocalizing VIP. Brief (minutes) application of selective PAR2 agonists, including trypsin, the activating peptide SL-NH2 and mast cell tryptase, evoked depolarizations of the submucosal neurons, as measured with intracellular recording techniques. The membrane potential returned to resting values following washout of agonists, but most neurons were hyperexcitable for the duration of recordings (> 30 min-hours) and exhibited an increased input resistance and amplitude of fast EPSPs. Trypsin, in the presence of soybean trypsin inhibitor, and the reverse sequence of the activating peptide (LR-NH2) had no effect on neuronal membrane potential or long-term excitability. Degranulation of mast cells in the presence of antagonists of established excitatory mast cell mediators (histamine, 5-HT, prostaglandins) also caused depolarization, and following washout of antigen, long-term excitation was observed. Mast cell degranulation resulted in the release of proteases, which desensitized neurons to other agonists of PAR2. Our results suggest that proteases from degranulated mast cells cleave PAR2 on submucosal neurons to cause acute and long-term hyperexcitability. This signalling pathway between immune cells and neurons is a previously unrecognized mechanism that could contribute to chronic alterations in visceral function.
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PMID:Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons. 1256 62

The neuropeptides substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) have been considered as important mediators in migraine and other primary headaches. CGRP and VIP have been found at increased concentrations in jugular venous plasma during attacks of migraine or cluster headache, and CGRP receptor antagonists have recently been shown to be effective in migraine therapy. Substance P and CGRP are produced from a subset of trigeminal afferents, whereas VIP derives from parasympathetic efferents. Release of these neuropeptides in the meninges can cause arterial vasodilatation, mast cell degranulation and plasma extravasation in animal experiments, but only CGRP seems to be relevant in migraine. Animal models have confirmed the important role of CGRP in meningeal nociception. The activity of spinal trigeminal neurons is a sensitive integrative measure of trigeminal activity and is partly under the control of CGRP, most likely via central mechanisms. CGRP released from central terminals of trigeminal afferents in the spinal trigeminal nucleus seems to facilitate nociceptive transmission via presynaptic mechanisms. The central effect of CGRP is substantiated by suppression of nociceptive c-fos activation and neuronal activity in the spinal trigeminal nucleus following CGRP receptor inhibition. These proposed functions are supported by the localization of CGRP receptor components in the rat cranial dura mater, trigeminal ganglion and spinal trigeminal nucleus. The currently available data indicate multiple sites of CGRP action in trigeminal nociception and the pathogenesis of migraine; however, central CGRP receptors are likely to be the essential targets in the treatment of migraine using CGRP receptor antagonists.
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PMID:Neuropeptide effects in the trigeminal system: pathophysiology and clinical relevance in migraine. 2197 27