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 reactivity of ocular mast cells is poorly characterized in man. Provocation tests with codeine phosphate, a molecule known to activate connective tissue mast cells, were performed in ten normal subjects. Ten-fold increasing concentrations of codeine phosphate (10(-5) to 10(-1) mg/mL) were tested in both eyes until a positive challenge was observed. Schirmer strips were placed under the eyelid and left for five minutes. A negative control was performed ten days later. All subjects had a strongly positive reaction for the same codeine phosphate concentration (10(-1) mg/mL). Histamine was released in 8/10 subjects (control: 7.06 +/- 4.19 nM/L, codeine phosphate: 18.2 +/- 15.7 nM/L, P < .018), PGD2 was released in 8/10 subjects (control: 0 codeine phosphate: 273.3 +/- 408.9 ng/L). Disodium cromoglycate blocked the release of histamine and PGD2. Codeine phosphate is potent at causing mast cell activation in the eye and this effect is blocked by disodium cromoglycate.
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PMID:Conjunctival provocation tests with codeine phosphate. Effect of disodium cromoglycate. 768 4

Nasal allergy is due to a change in the immunoreactivity of an individual. B-lymphocytes produce allergen-specific IgE antibodies after the antigen is presented to T-helper cells. IgE bound to mast cells leads to mast cell activation in the case of antigen contact. Mast cells release mediators and induce local inflammation. The symptoms of allergic rhinitis are caused by various factors and are different in individuals, and hence therapy must be in accordance with the necessities in the individual. There are four principles of therapy in allergic rhinitis. The first and best is allergen avoidance. It is the first choice in animal allergy and important in mite allergy. It is difficult for mold allergy and impossible for pollen allergy. The second is immunotherapy. Immunotherapy is a specific form of controlled allergen admission that changes immunoreactivity into allergen tolerance in a major part of patients. Immunotherapy is a very important tool if performed by a physician with experience. The third principle is drug therapy. With todays drugs, it is still symptomatic. alpha-sympathomimetic vasoconstrictors administered systemically (and, still better, locally) relieve nasal stuffiness. Parasympatholytic drugs can abort pathological secretions. Cromoglycate (DNCG) is a local prophylactic drug improving all symptoms of allergic rhinitis. DNCG is the first choice in pollinosis. Antihistamines are usually given systemically, and the modern drugs have no sedative effect. Clinical effects are comparable to DNCG, and there are new substances available for local therapy. Steroids given systematically improve all symptoms of allergy and inflammation after a certain delay. Due to side effects, local steroids are preferred today.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapy of allergic rhinitis]. 810 4

A close anatomical relationship between nerves containing substance P and calcitonin gene-related peptide (CGRP) and mast cells containing serotonin has been demonstrated in the rat lacrimal gland. This study investigates the potential for peptidergic regulation of lacrimal mast cells by examining the actions of substance P, CGRP and serotonin on protein and peroxidase secretion from isolated lacrimal segments and on substance P and CGRP to release serotonin from the lacrimal mast cells. Substance P, CGRP and serotonin evoked marked increases in total protein and peroxidase from the lacrimal. Sodium cromoglycate, a mast cell stabilizer, significantly reduced or blocked the secretory responses elicited by these agonists. Chromatographic analysis using electrochemical detection revealed that substance P, but not CGRP, augmented the release of serotonin from the gland. The substance P evoked peroxidase secretion and serotonin release was blocked by CGRP and by sodium cromoglycate. These results support a role for mast cells in the regulation of lacrimal secretion and suggest a novel regulatory interaction between substance P and CGRP in the control of lacrimal function through a neuro-immune interaction.
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PMID:Secretion and serotonin release in the isolated rat lacrimal gland: the effects of substance P and calcitonin gene-related peptide. 891 52

It has been proposed that the cardioprotective effects of myocardial ischaemic preconditioning may involve the release of mast cell mediators. The aim of the study was to determine whether mast cells are involved in the antiarrhythmic effect of ischaemic preconditioning in rat hearts. Preconditioning was achieved, both in anaesthetised rats and in rat isolated hearts, by a 3-min temporary occlusion of the left main coronary artery followed by 10 min of reperfusion before a 30-min permanent occlusion. Preconditioning had a marked antiarrhythmic effect, reducing the number of ventricular ectopic beats from 1,176 +/- 69 to 490 +/- 139 and the incidence of ventricular fibrillation from 40% to 0. Administration of the mast cell-stabilising drugs lodoxamide tromethamine and sodium cromoglycate (20 mg/kg/h i.v. 30 min before and throughout experimental protocol) did not modify the antiarrhythmic effect of preconditioning. Sodium cromoglycate, but not lodoxamide tromethamine, itself significantly reduced the number of ectopic beats that occurred over a 30-min period of ischaemia (from 760 +/- 181 to 153 +/- 33 in nonpreconditioned animals). Both drugs abolished the decrease in arterial blood pressure that occurred on coronary artery occlusion. The decrease in arterial blood pressure produced by the mast cell-degranulating compound 48/80 (50 microg/kg; i.v.) was attenuated to a similar degree by both drugs (decreases in pressure of 53 +/- 7, 31 +/- 1, and 25 +/- 3 mm Hg in control, sodium cromoglycate-treated, and lodoxamide tromethamine-treated animals, respectively). In rat isolated hearts, degranulation of mast cells with three consecutive doses of 50 microg of compound 48/80 had no antiarrhythmic effects and did not modify the antiarrhythmic effect of preconditioning. It is concluded that cardiac mast cells do not play a major role in the protection offered by ischaemic preconditioning on arrhythmogenesis in rat hearts.
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PMID:Lack of involvement of mast cell degranulation in the antiarrhythmic effect of preconditioning in rats. 951 87

Disodium cromoglycate (cromolyn) is a well documented inhibitor of immunologically-induced histamine release from rat peritoneal mast cells and has been shown to stimulate the phosphorylation of a mast cell protein of apparent molecular mass 78,000 Da (78 kDa), an event which may be involved in terminating secretion. Here we aimed to determine the role of the ubiquitous enzyme, protein kinase C, in the phosphorylating activity of cromolyn by examining the effects of phorbol esters (activators of protein kinase C) on protein phosphorylation in [32P]orthophosphate loaded rat peritoneal mast cells. Protein kinase C-activating phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) and 4beta-phorbol 12,13-dibutyrate (PdBu) were found to potently inhibit cromolyn-induced phosphorylation when added to mast cells simultaneously with cromolyn (IC50 22 and 79 nM respectively). 4Alpha-phorbol 12,13-didecanoate (PdD), a phorbol ester which does not activate protein kinase C, had no effect on cromolyn-induced phosphorylation. Addition of TPA to mast cells previously exposed to cromolyn for 60 sec (i.e. when 78-kDa protein phosphorylation is maximal) also caused a very rapid dephosphorylation of the 78-kDa protein. Phosphorylation of the 78-kDa protein can also be induced by dibutyryl cyclic GMP and this action was similarly inhibited by TPA and PdBu. Cromolyn inhibited secretion induced by anti-IgE, but not by TPA, and thus inhibition of secretion by cromolyn is further correlated to its phosphorylation of the 78-kDa protein. The data suggest that the inhibitory action of cromolyn on mast cell secretion and phosphorylation of the 78-kDa protein are not mediated through a phorbol ester-sensitive protein kinase C, but more likely that such an enzyme could be involved in regulating dephosphorylation of the 78-kDa protein. Further explanations for this novel dephosphorylating activity of phorbol esters are discussed.
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PMID:Inhibition of cromolyn-induced phosphorylation of a 78-kDa protein by phorbol esters in rat peritoneal mast cells. 951 69

The role of mast cells and their main secretory products in the effects of oestradiol on the uterus was investigated. Ovariectomized rats were treated with a single injection of oestradiol (10 micrograms per rat, i.m.) or vehicle together with drugs affecting the activity of mast cells, cromoglycate (10 mg per rat, i.m.), which diminishes the degranulation of mast cells, or compound 48/80 (0.5 mg per rat, i.m.), which enhances this process. Oestradiol or vehicle was also administered with two important secretory products of mast cells, heparin (0.4 mg per rat, i.m.) or histamine (2 mg per rat, i.m.). All drugs were injected simultaneously with oestradiol (first injection) and then every 6 h until the animals were killed. Observations were performed at 24, 36 and 48 h after oestradiol or vehicle injection. The condition of mast cells was determined by the percentage of degranulated mast cells in sections stained with toluidine blue. Oestradiol-induced effects in the uterus were estimated by the mitotic index, proliferating cell nuclear antigen-labelling index, DNA content, volumes of cells, nuclei and nucleoli in the luminal epithelium, glandular epithelium and stroma cells of the endometrium. Cromoglycate treatment resulted in a decrease in both mast cell degranulation and all examined oestradiol effects in the uterus at all periods of observation. Compound 48/80 increased mast cell degranulation and expression of one aspect of oestradiol effects on the volumes of cell compartments. Histamine or heparin led to a marked increase in the cell, nucleus and nucleolus volumes in all uterine structures. However, heparin produced a depression in proliferation, whereas histamine had a weak transient stimulating action on this process. No effects of the protocols were found in the absence of oestradiol treatment. These results suggest that mast cells are involved in the realization of oestrogen action, including the stimulation of cell growth and proliferation in the uterus, and that the effect of mast cells is mediated by both histamine and heparin.
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PMID:Role of mast cells in oestradiol effects on the uterus of ovariectomized rats. 971 77

Seasonal allergic conjunctivitis is rarely associated with permanent vision impairment; however, it is a relatively common condition that may compromise the quality of life. It may, in extreme cases, impair daily activities, including work. Numerous treatment options have become available for the relief of acute symptoms. Avoidance should always be the first line in therapy but, in most cases, is not practical, especially with pollen allergies. The use of saline eyedrops is simple and nontoxic, and it is effective in up to 30% to 35% of cases. It can and should be added to all other remedies to reduce adverse effects and cost by decreasing the need for other therapeutic options. Antihistamines and decongestants are useful treatment choices for the majority of cases. Ketorolac tromethamine may be helpful in relieving pruritus, but it offers little advantage over topical antihistamines. Corticosteroids may be used for severe cases for a limited time. If topical corticosteroids are being considered, an ophthalmologist should be consulted. Cromolyn sodium and lodoxamide ophthalmic solution may be helpful in the prophylaxis of symptoms during the allergy season, but these agents require frequent dosing. Olopatadine hydrochloride is a mast cell stabilizer and antihistamine that can be dosed twice a day. Immunotherapy is effective and should be offered to those who are intolerant or have allergic conjunctivitis refractory to medications.
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PMID:Seasonal allergic conjunctivitis: overview and treatment update. 1047 15

The objective of this study was to examine the role of mast cells and their principal product, histamine, in ischemia/reperfusion injury. Cromolyn sodium, diphenhydramine, and cimetidine were administered to ischemic flaps just before reperfusion and evaluated for flap survival, mast cell count, neutrophil count, and myeloperoxidase levels. Epigastric island skin flaps were elevated in 49 rats; they were rendered ischemic by clamping the artery for 10 hours. Thirty minutes before reperfusion, the rats were treated with intraperitoneal saline (n = 11), cimetidine (n = 11), diphenhydramine (n = 11), or cromolyn sodium (n = 10). Flap survival was evaluated at 7 days. Neutrophil counts, mast cell counts, and myeloperoxidase levels were evaluated 12 hours after reperfusion. Flap necrosis in the sham group of animals (n = 6) was 0.0 percent, as expected, whereas the control group (saline-treated animals) had 47.3+/-33.4 percent necrosis. Animals treated with diphenhydramine and cimetidine demonstrated a significant decrease in flap necrosis to 17.7+/-8.8 percent and 19.4+/-14.7 percent, respectively. This protective effect was not seen with cromolyn sodium (44.3+/-35.6 percent). Both neutrophil and mast cell counts were significantly decreased in flaps from antihistamine-treated and sham animals versus both saline- and cromolyn sodium-treated groups. The administration of diphenhydramine and cimetidine before reperfusion can significantly reduce the extent of flap necrosis and the neutrophil and mast cell counts caused by ischemia/reperfusion. This protective effect is not seen with cromolyn sodium. The protective effect of antihistamines on flap necrosis might be related to the decrease in neutrophils and, possibly, mast cells within the flap.
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PMID:Prevention of ischemia-reperfusion injury in a rat skin flap model: the role of mast cells, cromolyn sodium, and histamine receptor blockade. 1112 11

Compound 48/80 was applied into one eye of male Wistar rats and a drop of vehicle into the contralateral eye. Another group of rats received sodium cromoglycate in both eyes every 6 h for a period of 48 h. One eye was challenged with compound 48/80 30 min after the end of treatment with sodium cromoglycate. The eyes were monitored clinically and the histamine content of the conjunctiva was determined fluorometrically. The basal histamine levels in rat conjunctival homogenates were quantified. Pharmacologically-induced mast cell degranulation by a single application of 0.1 g ml(-1)of compound 48/80 resulted in significant decreases of conjunctival histamine levels 1, 12 and 24 h after challenge. Sodium cromoglycate prevented the effect of compound 48/80 when administered into the eye prior to the challenge with the non-immunogenic histamine releaser. Upon termination of the application, the membrane stabilizer was unable to reverse the reduced histamine levels in the conjunctival homogenates.
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PMID:Changes in histamine content following pharmacologically-induced mast cell degranulation in the rat conjunctiva. 1081 37

Disodium cromoglycate (cromolyn) inhibits mast cell secretion, but its mechanism has not been elucidated. One possibility is the phosphorylation of a 78-kDa mast cell protein, two fragments of which are homologous to moesin, a member of the ezrin, radixin, moesin family. These proteins appear to be involved in signal transduction by regulating functional associations between the cell surface and the cytoskeleton. Moesin cDNA was cloned from rat basophil leukemia cells, which are similar to mucosal mast cells, and polyclonal antiserum was prepared against recombinant moesin expressed in Escherichia coli. Moesin phosphorylated in mast cells treated with cromolyn shifted from the soluble to the precipitable fraction and associated with Sepharose-linked beta-actin. Recombinant moesin also associated with Sepharose-linked beta-actin, and so did purified RBL moesin, but only if the latter was first denatured. Moesin thus appears to have actin binding sites that are not exposed under normal conditions but may become available by in vivo phosphorylation or by denaturation. Immunocytochemistry using confocal microscopy showed moesin to be primarily localized on the inner aspect of the plasma membrane and around secretory granules. Double immunocytochemistry for moesin and actin colocalized them in most areas. Ultracryoimmunoelectron microscopy to preserve the antigenicity of moesin identified the protein close to the plasma and secretory granule membranes. Cromolyn appeared to induce clustering of moesin around secretory granules. It is hypothesized that conformational changes of moesin, regulated by phosphorylation/dephosphorylation, may lead to positional rearrangements with respect to the membrane/cytoskeleton that could possibly regulate mast cell secretion.
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PMID:Cloning and cellular localization of the rat mast cell 78-kDa protein phosphorylated in response to the mast cell "stabilizer" cromolyn. 1094 28


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