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 precise roles of carnosine and histamine in the physiologic response of the cardiovascular system to stress are unknown. We have previously shown in skeletal and cardiac muscle that carnosine serves as a histidine reservoir available for subsequent histamine synthesis following trauma and sepsis. This study was designed to quantify the effect of histamine-releasing and blocking agents on the myocardial carnosine-histamine pathway as well as on survival during severe stress. Four groups of mature (9-month-old) Sprague-Dawley rats were treated with either (1) saline, (2) lodoxamide (L, mast cell degranulation inhibitor), (3) compound 48/80 (a mast cell degranulator which causes stress), or (4) L followed by 48/80, and observed until agonal or the end of 30 min. When either endpoint was reached the animals were sacrificed and their hearts were removed for tissue analyses of histidine, histamine, 3-methylhistamine, and carnosine via high-pressure liquid chromatography. All five L-pretreated animals survived challenge with 48/80 while all five animals given 48/80 alone died (P less than .005). This mortality correlated well with the increase in the myocardial levels of histidine (P less than or equal to .0005), histamine (P less than or equal to .0077), and 3-methylhistamine (P less than or equal to .0004) and the decrease in carnosine (P less than or equal to .009) experienced by the animals treated with 48/80 alone in comparison to the control, L-only- and L + 48/80-treated groups. A protective effect of L was shown against the deleterious effects of 48/80 which is associated with prevention of myocardial carnosine mobilization to histidine and histamine. These data support the role of carnosine as a nontoxic myocardial histidine reservoir which is mobilized in response to stress-induced increases in histamine requirements.
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PMID:Improved survival from compound 48/80-induced lethal stress and inhibition of myocardial histamine and carnosine mobilization by lodoxamide. 270 50

Like the skin of rats and mice injected with adrenaline (AD), rat isolated peritoneal mast cells display increased levels of perchloric acid-soluble histamine following incubation with AD. Although pre-exposure to alpha-fluoromethyl histidine (FMH), an inhibitor of histidine decarboxylase, prevented the effect of AD in vivo and in vitro, this compound was also found to inhibit mast cell granule swelling evoked by AD, a response linked to histamine changes. Absence of increased levels of isotopic histamine in mast cells incubated with labelled histidine in the presence of AD, as well as the insufficient amounts of would-be precursor histidine found in untreated mast cells, confirm the conclusion that AD does not increase mast cell histamine by stimulating its synthesis.
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PMID:Increased levels of histamine observed in the skin of adrenaline-treated rats or mice are not the result of histamine synthesis by mast cells. 275 May 95

Both interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce increased histamine production by murine hemopoietic cells. Histidine-free culture conditions or addition of alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, completely abrogate this phenomenon, indicating that increased histamine levels result from an augmentation of the rate of its synthesis. L-Histidine decarboxylase (HDC) (EC 4.1.1.22) activity is detected in normal bone marrow cell lysates. It is markedly increased following incubation of the cells with IL-3 or GM-CSF. The cells responding by the most important enhancement of HDC activity are located in the less dense layers of a discontinuous Ficoll gradient containing the majority of the hemopoietic progenitor cell types, such as colony-forming units (spleen), granulocyte-macrophage colony-forming cells, and mast cell precursors. In comparison with other HDC-containing cell populations tested, the enzymatic activity contained in these cells is particularly high after IL-3 or GM-CSF treatment and similar to the HDC levels observed in murine fetal liver. The time course of IL-3 and GM-CSF-induced HDC activation at comparable concentrations is slightly different. In response to GM-CSF, HDC activation is more rapid, with a significant enhancement after 4 hr of incubation, as compared with IL-3-induced HDC activation. Moreover, in the latter case the activation increases more progressively up to 48 hr of incubation, whereas GM-CSF-induced increase of HDC activity reaches a plateau more rapidly. In addition, maximal increase in histamine production in response to IL-3 is always higher than in response to GM-CSF. Moreover, the simultaneous presence of both factors at optimal concentration induces only a partially cumulative effect. These results suggest that IL-3 and GM-CSF induce HDC activation in two distinct ways, possibly reflecting the involvement of distinct target cells. However, both mediators act by inducing the transcription of the HDC gene and de novo synthesis of this enzyme since actinomycin D or cycloheximide abolish GM-CSF-or IL-3-induced histamine-producing cell-stimulating activity. This synthesis is independent from cell proliferation as demonstrated by the lack of effect of bone marrow cell irradiation. Finally, the observation that cholera toxin, prostaglandin E2, and N6,2'-O-dibutyryl adenosine 3',5'-cyclic monophosphate mimic the effects of IL-3 and GM-CSF on bone marrow cell HDC suggests an involvement of cyclic adenosine monophosphate in factor-induced histamine-producing cell-stimulating activity.
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PMID:Histamine-producing cell-stimulating activity. Interleukin 3 and granulocyte-macrophage colony-stimulating factor induce de novo synthesis of histidine decarboxylase in hemopoietic progenitor cells. 282 13

In addition to cholinergic neural mechanisms, airway tone is influenced by adrenergic mechanisms and by more recently described neural mechanisms which are non-adrenergic and non-cholinergic (NANC). Sympathetic innervation to human airways is very sparse and there is no functional adrenergic innervation of smooth muscle, although sympathetic fibres may supply ganglia, submucosal glands and bronchial vessels. Airway tone may be influenced by circulating adrenaline and there is some evidence that adrenaline secretion may be impaired in asthma. beta-Adrenoceptors (which are almost entirely of the beta 2-subtype) are localized to many cell types in airways and beta-agonist may be beneficial in airway obstruction, not only by directly relaxing airway smooth muscle (from trachea to terminal bronchioles), but by inhibiting mast cell mediator release, by modulating cholinergic nerves, by reducing bronchial oedema and by reversing the defect in mucociliary clearance. There is little evidence that beta-receptor function is impaired in asthma. Alpha-adrenoceptors, which are bronchoconstrictor, may be activated by inflammatory mediators and disease, and alpha-agonists cause bronchoconstriction in asthmatic patients. However, alpha-antagonists have little effect, which questions the role of alpha-receptors in asthma. NANC nerves which relax human airways have been demonstrated in vitro. Although the neurotransmitter is not certain, there is now convincing evidence that it may be vasoactive intestinal peptide (VIP) and a related peptide histidine methionine (PHM). VIP and PHM immuno-active nerves are found in human airways, and both peptides potently relay human airways in vitro (but not in vivo because of diffusion and metabolism problems).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adrenergic and non-adrenergic, non-cholinergic control of airways. 303 86

This study allows the indirect demonstration of a precursor for TRH in pancreatic extracts of 2-days old rats. The sequential treatment of these extracts with trypsin and carboxypeptidase A is followed by a large increase in Pyroglutamyl Histidine Proline (TRH-OH). The molecular weight of the protein that gives rise to TRH-OH after enzymatic treatment ranges between 30,000 and 40,000 daltons. During ontogenesis. TRH levels decrease earlier and more rapidly than that of TRH-precursor levels. These data suggest that changes in the processing of TRH-precursor play a role in the diminution of TRH concentrations that is observed during the first two weeks of life.
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PMID:[Demonstration of a TRH precursor in the pancreas of the newborn rat]. 309 24

Solitary mastocytoma (mast cell naevus) of the skin represents a relatively rare dermal tumour. Its occurrence on the lower eyelid is exceptional. We report the case of a 4 month old male infant who exhibited a firm, yellowish nodule (1 cm in maximum diameter) on the lower lid of the right eye from birth. Histologically, the tumour consisted of strongly metachromatic tissue mast cells (TMC) infiltrating the whole dermis, the adjacent subcutaneous tissue and the lid muscle. Since comparable skin lesions in other sites were not observed, a diagnosis of solitary mastocytoma was made. Immunocytological investigations revealed strong reactivity of the TMC to antisera against vimentin, common leucocyte antigen (CLA), alpha 1-antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACT). A minor proportion of the TMC reacted to antisera against lysozyme and KiB3. Surprisingly, the TMC also reacted to antisera against certain regulatory peptides (RP), namely adrenocorticotropic hormone (ACTH), peptide histidine isoleucine (PHI), leu-enkephalin and met-enkephalin. However, absorption controls revealed that the immunostaining for ACTH and the two enkephalins was non-specific. The immunocytological phenotype of TMC suggests a close relationship to the myeloid-monocytic lineage, but a possible relationship between TMC and the diffuse neuroendocrine system needs further investigation.
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PMID:Solitary mastocytoma of the eyelid. A case report with special reference to the immunocytology of human tissue mast cells, and a review of the literature. 312 Apr 1

Three major 32P-labeled polypeptides were found in the soluble fraction of bovine lenses cultured in a medium containing [32P]orthophosphate. Two of the polypeptides corresponded to the phosphorylated A and B chains of alpha-crystallin. In this communication, the third polypeptide is now identified. This polypeptide is characterized by a molecular weight of 27,000 and a pI of 6.6, eluted exclusively in the beta Low fraction of a CL-6B gel filtration separation of lens soluble material, and could be further purified by DE52 anion exchange chromatography. The only 32P-labeled amino acid detected was phosphoserine. A single 32P-labeled peptide was observed after tryptic digestion and two-dimensional mapping. The amino acid sequence of the purified peptide is Gly-Ala-Phe-His-Pro-Ser-Ser. This sequence exactly matches the expected C-terminal tryptic fragment, residues 198-204, of the bovine beta-crystallin B2. The results of carboxypeptidase A digestion of the 32P-labeled peptide suggest that only Ser203 is phosphorylated. By using the catalytic subunit of the cAMP-dependent protein kinase, purified beta B2 was phosphorylated in vitro, generating a single 32P-labeled polypeptide with the identical pI as the phosphorylated polypeptide obtained from lens culture. On the basis of these data, the Mr 27,000 32P-labeled polypeptide is identified as the phosphorylated form of the beta-crystallin B2.
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PMID:Phosphorylation of beta-crystallin B2 (beta Bp) in the bovine lens. 317 May 71

P401 (also known as mast cell degranulating protein, MCD) is a minor component of honeybee venom. Its primary structure is related to that of apamin. We have studied the structure of P401 in solution by high-resolution two-dimensional 1H-NMR spectroscopy. Almost all the backbone proton resonances have been assigned by sequential assignment strategy. Analysis of NOEs shows that P401 has a conformation very similar to that of apamin. N-terminal residues Ile-1-Cys-5 are in an extended conformation and residues His-13-Asn-22 on the C-terminus are in an alpha-helical structure. These two secondary structural elements are connected by two tight turns.
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PMID:Structure of P401 (mast cell degranulating peptide) in solution. 323 81

The binding of L- and D-phenylalanine and carboxylate inhibitors to cobalt(II)-substituted carboxypeptidase A, Co(II)CPD (E), in the presence and absence of pseudohalogens (X = N3-, NCO-, and NCS-) has been studied by 1H NMR spectroscopy. This technique monitors the proton signals of histidine residues bound to cobalt(II) and is therefore sensitive to the interactions of inhibitors that perturb the coordination sphere of the metal. Enzyme-inhibitor complexes, E.I, E.I2, and E.I.X, each with characteristic NMR features, have been identified. Thus, for example, L-Phe binds close to the metal ion to form a 1:1 complex, whereas D-Phe binds stepwise, first to a nonmetal site and then to the metal ion to form a 2:1 complex. Both acetate and phenylacetate also form 2:1 adducts stepwise with the enzyme, but beta-phenylpropionate gives a 2:1 complex without any detectable 1:1 intermediate. N3-, NCO-, and NCS- generate E.I.X ternary complexes directly with Co(II)CPD.L-Phe and indirectly with the D-Phe and carboxylate inhibitor 2:1 complexes by displacing the second moiety from its metal binding site. The NMR data suggest that when the carboxylate group of a substrate or inhibitor binds at the active site, a conformational change occurs that allows a second ligand molecule to bind to the metal ion, altering its coordination sphere and thereby attenuating the bidentate behavior of Glu-72. The 1H NMR signals also reflect alterations in the histidine interactions with the metal upon inhibitor binding. Isotropic shifts in the signals for the C-4 (c) and N protons (a) of one of the histidine ligands are readily observed in all of these complexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:1H NMR spectroscopic characterization of binary and ternary complexes of cobalt(II) carboxypeptidase A with inhibitors. 324 89

A high-resolution x-ray crystallographic investigation of the complex between carboxypeptidase A (CPA; peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) and the slowly hydrolyzed substrate glycyl-L-tyrosine was done at -9 degrees C. Although this enzyme-substrate complex has been the subject of earlier crystallographic investigation, a higher resolution electron-density map of the complex with greater occupancy of the substrate was desired. All crystal chemistry (i.e., crystal soaking and x-ray data collection) was performed on a diffractometer-mounted flow cell, in which the crystal was immobilized. The x-ray data to 1.6-A resolution have yielded a well-resolved structure in which the zinc ion of the active site is five-coordinate: three enzyme residues (glutamate-72, histidine-69, and histidine-196) and the carbonyl oxygen and amino terminus of glycyl-L-tyrosine complete the coordination polyhedron of the metal. These results confirm that this substrate may be bound in a nonproductive manner, because the hydrolytically important zinc-bound water has been displaced and excluded from the active site. It is likely that all dipeptide substrates of carboxypeptidase A that carry an unprotected amino terminus are poor substrates because of such favorable bidentate coordination to the metal ion of the active site.
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PMID:X-ray crystallographic investigation of substrate binding to carboxypeptidase A at subzero temperature. 346 86


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