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)

An inhibitor of sodium-potassium-ATPase has been partially purified from the culture medium obtained from hypothalamic cells maintained in a capillary membrane perfusion system, and some of the properties of this inhibitory factor have been investigated. Gel filtration (Sephadex G-25 Superfine) of heat-treated medium (80 degrees C for 10 min) resulted in elution of inhibitory activity in the post-salt fraction. These fractions inhibited active (i.e. sodium-potassium-ATPase-mediated) sodium transport in intact human erythrocytes, displaced [3H]ouabain from its binding site, and directly inhibited canine kidney sodium-potassium-ATPase as measured by NADH oxidation. High-performance liquid chromatography (on Hypersil ODS) of these fractions after desalting yielded one region which showed inhibitory activity on all three assays. Inhibition of sodium-potassium-ATPase was dose-related and filtered through an Amicon UM10 membrane. Incubation of this material with dispase, carboxypeptidase A, chymotrypsin, and prolidase destroyed inhibitory activity, whereas trypsin and leucine aminopeptidase were ineffective. These studies show that hypothalamic neurones release a low molecular weight heat-stable peptide which inhibits active sodium transport, ouabain binding, and sodium-potassium-ATPase.
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PMID:Characterization and partial purification of the sodium-potassium-ATPase inhibitor released from cultured rat hypothalamic cells. 299 73

The co-operative response of regulated actomyosin ATPase to increasing concentrations of calcium has been attributed to nearest-neighbor interactions, presumably between troponin-tropomyosin complexes. The degree of co-operativity was not decreased after the carboxy-terminal 11 amino acid residues had been removed from tropomyosin by carboxypeptidase A. This indicates that the interactions between neighboring troponin-tropomyosin complexes do not occur through the overlapping tropomyosin ends.
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PMID:Removal of tropomyosin overlap and the co-operative response to increasing calcium concentrations of the acto-subfragment-1 ATPase. 315 45

Chicken gizzard tropomyosin was digested with carboxypeptidase A at the weight ratios of enzyme to substrate 1:200 and 1:50. Removal of about 16 C-terminal amino acid residues per tropomyosin molecule, at lower enzyme concentration, caused reversion of the effect on skeletal actomyosin ATPase activity from activating to inhibiting without an influence on polymerizability and actin-binding ability. Removal of about 26 C-terminal amino acid residues per molecule, at higher enzyme concentration, resulted in loss of polymerizability and actin binding ability. Digestion of gizzard tropomyosin with carboxypeptidase A has no dramatic effect on its binding to troponin T. The results show that not only the existence of head-to-tail overlapping regions but also their length is important for the functional properties of chicken gizzard tropomyosin.
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PMID:Properties of carboxypeptidase A-treated chicken gizzard tropomyosin. 315 33

1 Treatment of purified rat peritoneal mast cells at 37 degrees C with concentrations of the non-ionic detergent nonidet P40 (NP40) up to 0.005% (v/v) failed to reduce their viability. 2 There was a marked reduction in the histamine releasing capacity of NP40-treated mast cells upon challenge with a variety of selective (adrenocorticotrophic hormone 1-24 (Synacthen), rabbit anti-rat IgE antiserum, adenosine triphosphate (ATP) and the calcium ionophore, A 23187) and non-selective (rabbit anti-rat mast cell antiserum plus complement) histamine liberators. 3 Nonidet P40 (0.005%) was found to reduce the activity of a mast cell membrane 'ecto-enzyme', calcium-activated ATPase, by about 45% when presented at the time of its assay.
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PMID:The effects of nonidet P40 on the function of rat peritoneal mast cells in vitro. 616 28

The binding of 125I-labelled nonpolymerizable (brain or carboxypeptidase A-treated skeletal muscle) and polymerizable (intact skeletal muscle) tropomyosin to muscle F-actin was studied by ultracentrifugation under various conditions. The amount of nonpolymerizable tropomyosin bound to F-actin both in 0.1 M KCl and in 7 mM MgCl2 was much lower than that of the polymerizable one. In the presence of MgCl2 the amount of nonpolymerizable tropomyosin bound to F-actin approached saturation level. Under these conditions, however, the amount of skeletal muscle tropomyosin bound exceeded saturation, suggesting formation of both head-to-tail polymers and side-to-side aggregates. The latter seems to be responsible for the inhibition of acto-heavy meromyosin ATPase activity which is caused by skeletal muscle tropomyosin but not by nonpolymerizable tropomyosin. Nonpolymerizable tropomyosin can substitute for the rabbit skeletal muscle tropomyosin in the regulatory system operating in skeletal muscle. Inhibition of ATPase activity of acto-heavy meromyosin by nonpolymerizable tropomyosin in the presence of troponin and the absence of calcium ions is less than that obtained with polymerizable tropomyosin. The inhibition of ATPase activity is directly correlated with the extent of binding of nonpolymerizable tropomyosin to F-actin under the conditions of the ATPase assay.
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PMID:Some functional properties of nonpolymerizable and polymerizable tropomyosin. 622 47

The characteristics of vanadate-induced contraction of airways smooth muscle are described in isolated preparations of guinea-pig central and peripheral airways. Vanadate (1-1000 microM) induced sustained contractions of trachea and lung parenchymal strips within 1 min of challenge. It was more potent (P less than 0.001) on the lung strip (EC50 = 63 microM) than on the trachea (EC50 = 123 microM). The lung strip also developed greater maximum isometric tension (P less than 0.001) than the trachea. The efficacy on the lung strip was 2 and the trachea 0.6, relative to the response to acetylcholine (efficacy = 1). Vanadate-induced contractions of the trachea were not inhibited by atropine, mepyramine, phentolamine or indomethacin, nor after mast cell depletion by compound 48/80, showing that contractions were not mediated via specific receptors or by release of endogenous mediators of tone. Inorganic phosphate specifically inhibited vanadate responses in a dose-dependent and reversible manner, suggesting a common site of action. Contractions could be elicited in depolarized muscle and after treatment with ouabain plus propranolol, showing that membrane depolarization and inhibition of the Na, K-ATPase system were not involved in the contractile action of vanadate. Pretreatment of tracheal smooth muscle with verapamil had no influence on contractions elicited by vanadate. After removal of extracellular calcium, vanadate-induced contractions declined slowly with time, indicating that influx of extracellular calcium was not giving rise to contractions elicited by vanadate. Vanadate markedly increased the rate of calcium efflux from trachealis muscle loaded with 45Ca into both Ca2+-free and normal Krebs solutions; this is compatible with vanadate mobilizing an intracellular store of Ca2+. Such a store involving sites with Ca-ATPase activity would be consistent with the action of vanadate in isolated membrane preparations. Membrane-skinned tracheal fibres contracted by micromolar Ca2+ were relaxed by vanadate in a reversible dose-related manner, indicating that the contractile action of vanadate was not related to its interaction with proteins at the cross-bridge level.
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PMID:Mechanism of vanadate-induced contraction of airways smooth muscle of the guinea-pig. 665 67

Tubulin tyrosine ligase catalyzes the reversible addition of tyrosine to the C-terminus of tubulin alpha chains. By using ligase and carboxypeptidase A in conjunction, we have previously shown that brain cytoplasmic tubulin exists in three forms: 15-40% already has C-terminal tyrosine, another 10-30% can accept additional tyrosine, and about one-half is an uncharacterized species which is not a ligase substrate. A membrane-bound fraction of brain tubulin, purified by vinblastine precipitation from a detergent extract, has been found to differ by the complete absence of preexisting tyrosine. The membrane fraction from which tubulin was extracted also contained masked forms of both ligase and a distinct detyrosylating enzyme, which can be released by detergent extraction. The turnover of alpha-chain C-terminal tyrosine in vivo was studied by incubating brain mince with labeled tyrosine, or injecting it intracerebrally, under conditions where protein synthesis was inhibited. Tyrosine appeared to turn over to about the same extent in membrane-bound, as in soluble, tubulin. This apparently paradoxical result was not due to ATPase in the membrane fraction, which might have allowed ligase-catalyzed exchange between free and fixed tyrosine. Authentic [14C]tyrosylated tubulin added to the brain membrane fraction was not detyrosylated or subject to endoprotease digestion during subsequent procedures to isolate tubulin. The unexpected finding that tubulin tyrosylated at the C-terminal in vivo appears to be in the "non-substrate" fraction points toward a possible resolution of the paradox.
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PMID:An apparent paradox in the occurrence, and the in vivo turnover, of C-terminal tyrosine in membrane-bound tubulin of brain. 745 80

Two monoclonal antibodies, GLU-1 and A1.6, raised against gamma-L-glutamyl-L-glutamic acid dipeptide (Glu-Glu) and Ca(2+)-dependent ATPase from Paramecium, respectively, recognized the dipeptide Glu-Glu sequence. Whereas the antibodies immunofluorescently stained very few, if any, cytoskeletal fibers in cultured mammalian cells, almost all interphase as well as mitotic spindle microtubules became visible after treatment of cells with carboxypeptidase A. Immunoblot analysis demonstrated intense cross-reaction of the antibodies to the alpha-tubulin subunit. alpha-Tubulin isotypes produced as fusion proteins in bacteria were labeled by both the antibodies only when the proteins did not contain a tyrosine residue at the C terminus, indicating that GLU-1 and A1.6 specifically recognize the detyrosinated form of alpha-tubulin. When microtubule protein purified from brain was probed, not only alpha-but also, to a lesser extent, beta-tubulin were revealed by the dipeptide antibodies. A synthetic tripeptide YED containing one glutamyl group linked to the second residue of the peptide via the gamma position was also recognized by the antibodies. Since this peptide sequence corresponds to the amino acid sequence of polyglutamyated class III beta isotype at amino acid position 437 to 439, it is suggested that GLU-1 and A1.6 are able to recognize the glutamylated form of beta-tubulin. These results indicate that the C-terminal Glu-Glu sequence displays strong antigenicity, and the antibodies recognize the sequence present in the C terminus of the detyrosinated form of alpha-tubulin and the glutamyl side chain of beta-tubulin. Particularly strong immunoreaction was detected with ciliary and flagellar microtubules; thus, stable axonemal microtubules appear to be rich in post-translationally modified tubulin subunits.
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PMID:Monoclonal anti-dipeptide antibodies cross-react with detyrosinated and glutamylated forms of tubulins. 753 12

Cyclopiazonic acid has been reported to inhibit the Ca(2+)-ATPase of intracellular calcium stores in some nonexcitable cell types, such as myeloid cells and lymphocytes. The present study examines the effects of cyclopiazonic acid on rat basophilic leukemia (RBL) cells, a mucosal mast cell line. Addition of cyclopiazonic acid to fura-2-loaded RBL cells evoked a biphasic increase in free ionized intracellular calcium. Release of stored calcium accounted for the first phase of this response. The second phase was determined to be calcium entering through an influx pathway activated by cyclopiazonic acid. The influx pathway was selective for calcium, but was somewhat permeable to manganese. However, in a Ca(2+)-free solution containing EGTA, sodium ions permeated freely. This influx pathway appears to be identical to that which is activated by antigen, the physiological stimulus to the cells. Cyclopiazonic acid also induced secretion when combined with the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate, which activates protein kinase C.
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PMID:Ca(2+)-ATPase inhibitor, cyclopiazonic acid, releases Ca2+ from intracellular stores in RBL-2H3 mast cells and activates a Ca2+ influx pathway that is permeable to sodium and manganese. 779 Mar 92

We examined the inhibitory effect of DS-4574 (6-(2-cyclohexylethyl)[1,3,4]thiadiazolo[3,2-alpha]-1,2,3- triazolo[4,5-d] pyrimidin-9(3H)-one), a mast cell stabilizer with peptidoleukotriene receptor antagonism, on gastric acid secretion stimulated by several secretagogues in rats. In anesthetized rats with acute gastric fistulas, DS-4574 (50 mg/kg, intraduodenal) significantly inhibited gastric acid secretion induced by both carbachol (50 micrograms/kg, s.c.) and pentagastrin (75 micrograms/kg, s.c.) but not by histamine (2.5 mg/kg, s.c.). In unanesthetized pylorus-ligated rats, DS-4574 (10 and 25 mg/kg, intraduodenal) markedly suppressed increases in gastric acid output and histamine leakage into the gastric juice produced by carbachol (0.1 mg/kg, s.c.) or pentagastrin (1 mg/kg, s.c.). When the relationship between acid output and histamine leakage elicited by carbachol and pentagastrin was assessed, there was a close correlation (r = 0.84) that was highly significant (P < 0.01). In the in vitro study with rat gastric tissues, DS-4574 (10(-7)-10(-5) M) had no effect on the K(+)-dependent ATPase activity or on aminopyrine uptake into mucosal preparations containing parietal cells stimulated by carbachol (10(-5) M), histamine (10(-4) M), or dibutyryl-cyclic AMP (10(-3) M). These results suggest that the effect of DS-4574 may be mediated by inhibition of endogenous histamine from histamine-storing cells in the stomach.
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PMID:Inhibitory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene receptor antagonism, on gastric acid secretion in rats. 802 47


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