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)

It had been reported by authors that salivary gland hormone, parotin, was composed with subunit (parotin-subunit) which showed molecular weight of 45,000, and that parotin-subunit had rabbit serum calcium decreasing activity and the cross reactivity with rabbit anti parotin serum. In the present report, in order to study physiological chemistry of parotin-subunit, the influence of parotin-subunit on serum Ca and 45Ca levels relating to calcium metabolism, the distribution of 131I-parotin-subunit, the effect of parotin-subunit, on adenyl cyclase-cyclicAMP system, the anabolic action, C-terminal amino acid sequence and sugar component of parotin-subunit were investigated. The results are summarized as follows: 1) The decrease of rabbit serum Ca after injection of parotin-subunit was related to change of Ca in stable bone, but not to inhibition of bone resorption. 2) A high concentrated localization of radioactivity of 131I-parotin-subunit was found in liver, kidney and spleen, and as much as 60% of administrated radioactivity was localized in liver at 5 min after the injection. The retention of radioactivity was found in testis, seminal vesicle, prostate, parotid gland and submaxillary gland. 3) Cyclic AMP level increased significantly in metaphysial bone, submaxillary gland and plasma after administration of parotin-subunit but in other organs with localized much radioactivities, the level did not changed. Parotin-subunit activated adenyl cyclase of particular fraction of metaphysial bone. 4) The C-terminal amino acid of parotin-subunit was Leu, and its C-terminal amino acid sequence was -Val-Ser-Ala-Thr- Leu-OH by digestion of carboxypeptidase A. 5) Parotin-subunit included 3.3% of sugar which consisted of amino sugar and uronic acid.
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PMID:[The study of physiological chemistry on a subunit of salivary gland hormone (2) (author's transl)]. 18 2

Glucagon1-21 has been prepared by treating native glucagon with carboxypeptidase A. Purified glucagon1-21 did not contain detectable methionine (less than 0.001 residue/mol) and the activity of the compound did not change after treatment with cyanogen bromide as has been shown with native glucagon. Glucagon1-21 stimulates hepatic adenylate cyclase activity to the same extent as native glucagon but with 0.1% the potency. Glucagon1-21 also displayed 0.1% the binding affinity of native glucagon to the glucagon receptor in hepatic membranes. Glucagon22-29 alone or in combination with glucagon1-21 did not activate adenylate cyclase or displase 125I-glucagon from its receptor. The finding that glucagon1-21 is a full agonist on adenylate cyclase is discussed in relation to the structure-function relationships required for the biological action of glucagon.
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PMID:A reassessment of structure-function relationships in glucagon. Glucagon1-21 is a full agonist. 21 Jan 80

Mast cells are hypothesized to participate in processes leading to tissue fibrosis in human lung and skin. To explore the possible involvement of mast cell mediators in fibrogenesis, the mitogenic activity of mast cell tryptase from human lung was examined in vitro. The results indicate that human tryptase is a potent inducer of DNA synthesis in fibroblasts from multiple sources, including human lung. As demonstrated by mitogenic responses in fibroblasts, but not in vascular smooth muscle cells, tryptase is a mitogen with target cell specificity. Additionally, specificity is demonstrated by the differences in mitogenic activity of tryptase in comparison with thrombin, a structurally related mitogenic proteinase. Examination of the mitogenic effects of tryptase in the presence of other mitogens reveals synergy with mitogens that act through receptors coupled to intrinsic tyrosine kinases (insulin, epidermal growth factor, and basic fibroblast growth factor) or to G proteins (thrombin and serotonin). In the latter case, studies in Chinese hamster lung fibroblasts using specific receptor agonists and antagonists or receptor-transfected cell lines reveal a requirement for the activation of a G protein (Gi) negatively coupled to adenylate cyclase to act synergistically with tryptase. These data establish that human tryptase is a potent and specific mitogen in vitro and suggest that mitogenic signals generated by tryptase can interact synergistically with signals generated by both tyrosine kinase-coupled and G protein-coupled growth factor receptors.
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PMID:Human tryptase as a potent, cell-specific mitogen: role of signaling pathways in synergistic responses. 159 Apr 4

5'-(N-Ethyl)carboxamidoadenosine (NECA), an analog of adenosine, transiently stimulated a rat tumor mast cell (RBL-2H3 cells) to cause a release of inositol phosphates and an increase in levels of Ca2+ in the cytosol. It failed, however, to stimulate a sustained uptake of 45Ca2+ or secretion. The effects of other agents that act on P1- or P2-purinergic receptors suggested that NECA and other adenosine agonists acted via a novel subtype of adenosine membrane receptor. Although the order of potency of agonists was characteristic of A2-adenosine receptors, there was no indication of the involvement of adenylate cyclase, and antagonists such as isobutylmethylxanthine, 8-phenyltheophylline, and 8-p-sulfophenyltheophylline inhibited the responses to either NECA or antigen. The fact that stimulation of inositol phospholipid hydrolysis by NECA in washed, permeabilized RBL-2H3 cells was blocked by pertussis toxin as well as by cholera toxin suggested instead that the NECA-sensitive receptor activated phospholipase C via a G-protein. In contrast to NECA, antigen stimulation resulted in a pertussis toxin-resistant, sustained hydrolysis of inositol phospholipids, increases in free intracellular Ca2+, accelerated influx of 45Ca2+, and secretion from RBL-2H3 cells. In combination with NECA, all responses to antigen were markedly enhanced, and the enhancement was selectively blocked by pertussis toxin. The ability of antigen, but not NECA, to provoke secretion may be dependent primarily on the sustained activation of a cholera toxin-sensitive Ca2+ influx pathway that serves to amplify stimulatory signals for secretion. These studies also suggested that phospholipase C could be activated through different G-proteins via different receptors within the same cell.
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PMID:Activation of phospholipase C via adenosine receptors provides synergistic signals for secretion in antigen-stimulated RBL-2H3 cells. Evidence for a novel adenosine receptor. 229 18

There is now compelling evidence to incriminate bronchial mast cells in the pathogenesis of bronchoconstriction of allergic asthma. Human mast cells isolated from lung tissue or bronchoalveolar lavage release histamine and generate eicosanoids upon IgE-dependent activation. In this paper we present data that raise doubts about the significance of phospholipid methylation in IgE-dependent activation-secretion coupling and provide evidence that drugs such as 3-deazaadenosine inhibit mediator secretion by inhibiting phosphodiesterase, in addition to inhibiting putative methylation pathways. Activation of human mast cells and basophils also stimulates adenylate cyclase to increase levels of cyclic AMP, which, on the basis of pharmacological manipulation with purine nucleosides, we believe is involved in the progression of the secretory response. Human lung cells also generate both cyclo- and lipoxygenase products of arachidonate upon Ca++-dependent stimulation with complex interactions occurring between these pathways in the presence of the leukotriene inhibitor, Piriprost. The role of mast cells in the immediate airway response to inhaled allergens in asthma was demonstrated by showing an interaction between nonspecific bronchial reactivity and mast cell reactivity in predicting the airway response upon antigen inhalation. Further confirmation of this concept was obtained by showing an inverse relationship between the release of histamine and neutrophil chemotactic factor (NCF) into the circulation induced by antigen challenge, and nonspecific airway reactivity. The identification of significant increases in circulating mediators following antigen provocation of patients with seasonal asthma enabled the effects of drugs used in the treatment of asthma to be compared on airway calibre and mast cell mediator release. Sodium cromoglycate partially inhibited the airway and plasma histamine responses with antigen, but totally inhibited the increases in NCF. Salbutamol completely inhibited all responses, while ipratropium bromide, which produced the same bronchoconstriction as achieved with salbutamol, had no effect. The potent H1-antagonist astemizole partially inhibited bronchoconstriction without affecting histamine release. Antigen provocation produced a significant increase in circulating levels of the 13,14-dihydro-15-keto metabolite of PGF2 alpha which could originate from mast cell-derived PGD2. In both retrospective and prospective studies, a close relationship was shown between nonspecific bronchial reactivity and resting airway calibre in asthma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationship between mediator release from human lung mast cells in vitro and in vivo. 240 26

Forskolin, a diterpene compound isolated from the roots of Coleus forskohlii, activates adenylate cyclase in membranes from a variety of mammalian tissues. We found that forskolin (10(-7) to 3 X 10(-5) M) caused a concentration-related inhibition of IgE-mediated release of histamine and peptide leukotriene C4 (LTC4) from human basophils and lung mast cells. There was a significant linear correlation between the per cent inhibition of histamine and LTC4 release from both cell types. However, in both systems forskolin exerted a significantly greater inhibitory effect on LTC4 release than on histamine release. The concentration-response inhibition curve was paralleled by a forskolin-induced rise in cAMP levels in human leukocyte and mast cell preparations. The relationship between the effect of forskolin and the cAMP concentration was supported by the finding that forskolin inhibited the "first stage" of antigen-induced histamine release, but not the release caused by the Ca2+ ionophore, A23187. Propranolol, a competitive beta-receptor antagonist, did not block the inhibition of mediator release or the cAMP accumulation caused by forskolin. These data suggest that forskolin modulates the release of mediators of immediate hypersensitivity reactions via the activation of adenylate cyclase in human basophils and mast cells.
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PMID:Inhibition of IgE-mediated release of histamine and peptide leukotriene from human basophils and mast cells by forskolin. 243

The effects of adenosine and its analogues on cAMP-responses and histamine release of rat peritoneal mast cells were investigated. The adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA') activates the adenylate cyclase of the mast cell membranes and elevates the cAMP-levels of the intact mast cells. Both effects are antagonized by methylxanthines, suggesting that they are mediated via an A2 adenosine receptor. Adenosine and its analogues enhance the release of histamine from these cells, when the release is stimulated either by the calcium ionophore A 23187 or by concanavalin A. However, this effect is not antagonized by theophylline or 8-phenyltheophylline. In contrast, it is antagonized by the adenosine uptake blockers S-(p-nitrobenzyl)-6-thioinosine (NBTI) and S-(p-nitrobenzyl)-6-thioguanosine (NBTG). It is concluded that adenosine has two different effects on mast cells: it activates adenylate cyclase via an A2 adenosine receptor, and it enhances histamine release via an action at an intracellular site.
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PMID:Dual actions of adenosine on rat peritoneal mast cells. 244 Dec 69

The present study was undertaken to evaluate the effect of fenoterol, a selective beta 2-adrenergic agonist, on basophil histamine release. Fenoterol at 10(-7) to 10(-3) M did not inhibit the release of histamine induced by Dermatophagoides farinae extract (D.f.) from leukocytes from allergic patients sensitive to mite. Similarly, there was no suppression of histamine release induced by anti-IgE and formyl-methionyl-leucyl-phenylalanine under the influence of fenoterol. Fenoterol caused a slight inhibition of the calcium ionophore A23187-induced histamine release at 10(-3) M with % inhibition of 11.8 +/- 2.4 (means +/- SEM, P less than 0.05). There was no synergism between fenoterol and theophylline in inhibiting D.f.-induced histamine release. Fenoterol did not suppress the release of histamine induced by antigen at low as well as high levels of release. Based on the data on the effect of fenoterol on IgE-mediated histamine release, it was concluded that in contrast to a human lung mast cell system, the beta-adrenergic receptor-adenylate cyclase system is not a control mechanism in IgE-mediated basophil histamine release.
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PMID:Fenoterol, a selective beta 2-adrenergic agonist, and inhibition of IgE-mediated basophil histamine release. 244 20

Immunologic activation of purified human lung mast cells (HLMC) and basophils with anti-IgE induced histamine release but failed to elicit any changes in cAMP levels. In contrast, histamine release and monophasic rises in cAMP were observed in both rat peritoneal mast cells (RPMC) challenged with concanavalin A (73% enhancement over basal cAMP 20 sec after activation) and a cultured mouse bone marrow-derived mast cell (PT18 cell line) passively sensitized with dinitrophenol-specific IgE and stimulated with antigen (39% increase above basal at 15 sec). The adenylate cyclase activators isoprenaline, prostaglandin E2 (PGE2), and forskolin and the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) all induced elevations in cAMP levels in both basophils and HLMC. In basophils, PGE2 and isoprenaline produced approximately twofold increases in cAMP that were maximal at 1 min and decayed thereafter. Forskolin and IBMX produced threefold increases in cAMP that peaked 10 min after activation and persisted for up to 20 min. In HLMC, isoprenaline provoked a rapid monophasic fourfold increase in cAMP that was maximal at 1 min after addition. Levels of cAMP subsequently declined but remained significantly elevated over resting levels for up to 30 min. PGE2, forskolin, and IBMX all produced approximately threefold rises in HLMC cAMP that peaked around 5 min and persisted for 30 min. In both the basophil and HLMC, agonist-induced elevations in cAMP correlated well with the inhibition of mediator release. In basophils, the order IBMX greater than forskolin greater than PGE2 greater than isoprenaline held for both the inhibition of histamine and leukotriene C4 release and the augmentation of cAMP levels. In HLMC, individual agonists elevated cAMP levels to similar degrees and inhibited the release of histamine, leukotriene C4, and PGD2 to comparable extents, although the release of the arachidonate metabolites was generally more sensitive to the inhibitory actions of these agonists. These results suggest that elevations in cAMP, in both the basophil and HLMC, are associated with the inhibition of mediator release but not the initiation of the secretory process.
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PMID:Regulation of human basophil and lung mast cell function by cyclic adenosine monophosphate. 244 82

Enhanced phospholipid methylation has been suggested to be an obligatory process in IgE-dependent stimulus-secretion coupling in human lung mast cells. Our studies with mast cell-enriched lung preparations do not support this hypothesis, demonstrating no increased 3H-methyl radiolabeling of chloroform/methanol-extracted lipids or chromatographically separated phospholipids accompanying anti-IgE-dependent histamine secretion. Inhibitors of transmethylation, 3-deazaadenosine, and homocysteine thiolactone inhibited histamine secretion by both anti-IgE and calcium ionophore A23187, reflecting a requirement of secretion for overall integrity of cellular transmethylation. These agents induced small increases in cAMP concentration which are considered to make at most a minor contribution to this inhibition. The inability of methylation inhibitors to diminish anti-IgE-dependent increases in lung mast cell cAMP levels would suggest that not only does phospholipid methylation have no role in histamine secretion but also it does not participate in the activation of adenylate cyclase by this stimulus.
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PMID:IgE-dependent activation of human lung mast cells is not associated with increased phospholipid methylation. 245 37


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