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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine receptors on mouse bone marrow-derived mast cells were identified by functional criteria and radioligand binding. The stimulated release of beta-hexosaminidase from these cells was significantly augmented by the simultaneous addition of secretagogue and adenosine, NECA, or L-PIA. Similar enhancement of pre-formed mediator release occurred after a 10-min preincubation with adenosine. Resting mast cell cAMP levels increased within 15 sec after the addition of adenosine, and remained elevated for at least 60 sec. Although the antigen-or A23187-induced release of beta-hexosaminidase was markedly potentiated by exogenous adenosine, the stimulated release of [14C]-labeled arachidonic acid metabolites was minimally affected by adenosine, suggesting a differential effect of adenosine on granule-associated release as compared to generated mediator release. Bone marrow mast cells exhibited 5470 +/- 740 [3H]adenosine binding sites/cell, with a binding affinity of 24.4 +/- 3.8 nM. Cells cultured in the presence of 100 microM aminophylline for 6 days were hyperresponsive to exogenous adenosine, releasing a maximum of 162% of the amount of beta-hexosaminidase released from control cells in the presence of adenosine. The number of [3H]adenosine binding sites on the xanthine-treated cells increased to 156% of control values, suggesting an up-regulation of adenosine receptors induced by chronic exposure to an adenosine receptor antagonist. Mouse bone marrow mast cells possess functionally significant adenosine receptors that are regulated by aminophylline and that, when stimulated, produce many alterations in the mast cell secretory process.
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PMID:Adenosine receptors on mouse bone marrow-derived mast cells: functional significance and regulation by aminophylline. 633 Feb 5

Challenge of rat peritoneal mast cells with anti-rat IgE induces a similar pattern of protein phosphorylation to that already reported for compound 48/80. Rapid phosphorylation of a mast cell protein, mol. wt 78,000, is induced by sodium cromoglycate and several chemically related anti-allergic agents in the absence of any challenge. Phosphorylation of this protein reflects their potency in inhibiting anti-IgE-induced histamine release. Compounds which inhibit histamine release by elevating intracellular cAMP levels do not induce phosphorylation. However, dibutyryl-cGMP induces phosphorylation of the 78,000 mol. wt protein in the absence of any challenge, at concns which inhibit IgE-dependent histamine release. Sodium cromoglycate appears to activate an endogenous control mechanism for switching off mediator release using a mechanism mediated by cGMP.
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PMID:Phosphorylation of a mast cell protein in response to treatment with anti-allergic compounds. Implications for the mode of action of sodium cromoglycate. 640 82

Chymase, the major neutral protease of the rat serosal mast cell (RMC) secretory granule, causes RMC to release their secretory granules and to oxidatively metabolize endogenous arachidonic acid to prostaglandin D2 (PGD2). The granule markers, endogenous beta-hexosaminidase and exogenously added [3H]serotonin, were released from 2.5 X 10(5) RMC in 50 microliters in parallel and in dose-response fashion, reaching a maximum net percent release of approximately 50% with 0.5 to 1.0 units chymase (15 U/mg)/ml. With incremental concentrations of chymase, the release of granule markers occurred with a shorter lag period and in a greater maximal net percent, whereas the release of PGD2 was dose-related without a reduction in latency to detectable generation. Inhibition of the esterase activity of chymase with lima bean trypsin inhibitor decreased the subsequent mast cell response, indicating that the active site of chymase was required to initiate granule secretion and PGD2 generation. The monophasic indomethacin-resistant rise in cellular cAMP at 15 to 45 sec coincident with the onset of chymase-induced mediator release and PGD2 secretion is similar to that observed with IgE receptor-initiated coupled activation-secretion. The ability of heparin to block the activation function of chymase without inhibition of esterase activity reveals a possible physiologic regulatory mechanism for limiting the potential action of secreted chymase.
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PMID:Activation of rat serosal mast cells by chymase, an endogenous secretory granule protease. 642 8

Effect of the new theophylline derivative (beta-hydroxy-benzylopiperazinopropyl-theophylline), designed as R6 on degranulation of the mast cells from rat mesenteries, was tested in vitro and in vivo. In vitro it was found that R6 significantly inhibited mast cell degranulation induced both by the histamine liberator C 48/80 and by rabbit globulin directed against rat serum proteins. The effect was comparable to that revealed by mepyramine, but much stronger than the effects of DSCG and aminophylline. The influence of R6 on mast cells degranulation was less pronounced in the in vivo systems. It was demonstrated by histochemical methods that R6 did not change activity of lactic and succinic dehydrogenases, neither activity of lysosomal hydrolases. In separate system including small intestine from rat it was shown that R6 inhibited activity of the phosphodeisterase in smooth muscles. It was suggested that the effect of R6 on mast cells degranulation is mediated by an increase in cAMP as well as by indirect influence on Ca++ influx.
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PMID:Effect of the new theophylline derivatives on degranulation of mast cells and phosphodiesterase activity in smooth muscles. 677 54

Regulation of steel factor (SF) production in Sertoli cells from postnatal mouse testes was studied in a mast cell-Sertoli cell coculture system. Treatment of Sertoli cells with dibutyryl cAMP (50-1000 mumol l-1), forskolin (1-25 mmol l-1), and cholera toxin (10 micrograms ml-1) increased SF production, whereas FSH and theophylline had no significant effect. Furthermore, growth factors and testosterone, which would play some roles in spermatogenesis, were also tested, but none of these stimulated SF production. The constitutive production of SF may, rather, reflect the physiological condition of Sertoli cells in vivo.
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PMID:Effects of hormones, cyclic AMP analogues and growth factors on steel factor (SF) production in mouse Sertoli cell cultures. 750 77

Extracellular adenosine 5'-triphosphate (ATP) induced a characteristic, dose-dependent release of histamine and prostaglandin D2 (PGD2) from rat peritoneal mast cells. The process was relatively slow, non-cytotoxic, maximal at physiological pH and dependent on external calcium. Strontium and barium ions were able to substitute for calcium, although higher concentrations were required for maximal release. Cells stimulated in the absence of calcium progressively lost the ability to respond to subsequent reintroduction of the cation. The secretion of histamine induced by ATP was largely unaffected by the anti-asthmatic drugs disodium cromoglycate and nedocromil sodium but was inhibited by structurally related flavonoids and by cAMP-active drugs. Importantly, the non-hydrolysable guanosine 5'-triphosphate (GTP) analogue, GTP-gamma-S, elicited a dose-dependent release of histamine when introduced into mast cells permeabilized with ATP in the absence of external calcium. ATP thus appears to be a useful cell permeabilizing tool with which to study the biochemical processes involved in mast cell activation.
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PMID:Some characteristics of the ATP-induced histamine release from and permeabilization of rat mast cells. 751 69

Adenosine potentiates mast cell activation, but the receptor type and molecular mechanisms involved have not been defined. We, therefore, investigated the effects of adenosine on the human mast cell line HMC-1. Both the A2a selective agonist CGS21680 and the A2a/A2b nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased cAMP, but NECA was fourfold more efficacious and had a Hill coefficient of 0.55, suggesting the presence of both A2a and A2b receptors. NECA 10 microM evoked IL-8 release from HMC-1, but CGS21680 10 microM had no effect. In separate studies we found that enprofylline, an antiasthmatic previously thought to lack adenosine antagonistic properties, is as effective as theophylline as an antagonist of A2b receptors at concentrations achieved clinically. Both theophylline and enprofylline 300 micro completely blocked the release of IL-8 by NECA. NECA, but not CGS21680, increases inositol phosphate formation and intracellular calcium mobilization through a cholera and pertussis toxin-insensitive mechanism. In conclusion, both A2a and A2b receptors are present in HMC-1 cells and are coupled to adenylate cyclase. In addition, A2b receptors are coupled to phospholipase C and evoke IL-8 release. This effect is blocked by theophylline and enprofylline, raising the possibility that this mechanism contributes to their antiasthmatic effects.
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PMID:Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. 756 91

Releasability of mast cells and basophils to an IgE-dependent stimulus is regulated by extra- and intracellular factors which are only partly understood. As gangliosides are known to modulate receptor-dependent processes in various cell types, we have evaluated the effect of these molecules on mast cell mediator release. Human skin mast cells and the human mast cell line HMC1 were pretreated with the gangliosides GM2, GM3 and GD1a as well as with asialo-GM3, heparin and buffer alone (controls). After washing, the cells were stimulated with anti-IgE, calcium ionophore A 23187, N-FMLP or substance P. All gangliosides but not asialo-GM3 and heparin augmented anti-IgE-induced mediator release in a dose-dependent fashion, whereas the release to A 23187, N-FMLP and substance P remained unaffected. Only sequential but not simultaneous addition of ganglioside and anti-IgE showed an enhancement in mediator release compared to controls. Mediator release in both ganglioside-pretreated cells and controls was calcium-dependent and could be inhibited by pretreatment of cells with staurosporine or dibutyryl cAMP, indicating an unchanged signal transduction. Gangliosides appear to specifically optimize IgE-receptor-ligand interaction and alterations in cellular gangliosides could thus induce enhanced releasability as observed in atopics.
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PMID:Gangliosides enhance IgE receptor-dependent histamine and LTC4 release from human mast cells. 757 75

Adenosine activates adenylate cyclase and phospholipase C in mast cells and potentiates stimulated mediator release. To determine whether activation of adenylate cyclase is necessary for the effects of adenosine on the mast cell secretory process, a specific inhibitor of cAMP-dependent protein kinase, KT5720, was used. Antigen and adenosine each induced a rapid increase in mast cell cAMP-dependent protein kinase activity within 30 s. Preincubation with KT5720 (100 nM-10 microM) suppressed cAMP-dependent protein kinase activity and inhibited antigen-stimulated beta-hexosaminidase and leukotriene C4 releases. Adenosine retained its ability to potentiate beta-hexosaminidase release in antigen- and A23187-stimulated cells even in the presence of complete cAMP-dependent protein kinase inhibition. Mast cells rendered unresponsive to adenosine-related signals by preincubation with adenosine analogs maintained this hyporesponsiveness after incubation with KT5720. It appears that the abilities of adenosine to augment mast cell degranulation and induce receptor hyporesponsiveness are independent of changes in cAMP.
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PMID:Inhibition of protein kinase A fails to alter mast cell adenosine responsiveness. 774 Oct 46

Mast cells, which are capable of releasing a multitude of preformed and newly generated biological mediators and cytokines, are involved in various inflammatory processes. We studied whether histamine, a mast cell degranulation product, influences the adhesive interactions of T cells with extracellular matrix (ECM) glycoproteins, an event that occurs at sites of inflammation and is mediated primarily by virtue of cell-surface receptors of the beta 1-integrin subfamily. A prerequisite of lymphocyte-ECM interactions is activation of the cells, which modulates the affinity of the otherwise inactive integrins. Isolated rat CD4+ T cells were preincubated with histamine and activated with phorbol myristate acetate (PMA), and their ability to adhere to immobilized ECM components (fibronectin and laminin) was determined. Preincubation with histamine resulted in a 40-50% decrease in the adhesion of the CD4+ cells to both fibronectin or laminin. The notion that inhibition of T cell adhesion to ECM proteins by histamine-induced increase of the cells' intracellular levels of cAMP, thus interfering with calcium influx-associated events that occur during T cell activation, is supported by the finding that T cell adhesion was also abrogated by pharmacological inducers of cAMP. When the T cells were preincubated with supernatants of immunologically activated mast cells and then activated with PMA, a 40-50% inhibition of their adhesion to fibronectin or laminin was also observed. The inhibitory moiety present in the mast cell degranulation supernatants was resistant to heat (80 degrees C). Histamine exerted its suppressive effect on adhesion of T cells via their H2 receptors, as pretreatment with H2 antagonists abrogated the inhibitory effect. Thus, both purified histamine and mast cell-secreted histamine appear to be capable of affecting T cell interactions with ECM.
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PMID:Inhibition of T cell adhesion to extracellular matrix glycoproteins by histamine: a role for mast cell degranulation products. 793 Sep 46


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