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

Rats were maintained on a magnesium-deficient diet for 1 to 5 weeks to study the mast cell (MC) populations in their duodenum and kidney. A marked increase of intestinal subepithelial mast cells was observed in these animals as compared with normal controls. The cells in both groups showed an identical reaction for mucopolysaccharides but the 5-hydroxytryptamine content tended to be higher in the cells of magnesium-deficient animals. Proliferation of MC was also observed in the renal cortex of the magnesium-deficient rats. This finding is significant because MC are known to be virtually absent from normal kidneys. Magnesium deprivation resulted in numerous MC not only in the intertubular spaces but also within the glomeruli. Possible correlations between these and other pertinent observations are discussed with regard to certain renal diseases. The discussion is extended to the possible mechanism through which magnesium could influence secretory processes in MC.
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PMID:Mast cell increase in the duodenum and kidney of magnesium-deficient rats. 4 55

A crude plasma membrane fraction from the homogenate of purified rat mast cells demonstrates a high degree of Ca2+-dependent and Mg2+-dependent adenosine triphosphatase (ATPase) activity. The microsomal and mitochondrial fractions show negligible amounts of the Ca2+ and Mg2+-activated ATPases. The broad ATPase inhibitor, ethacrynic acid, effectively blocks the mast cell ATPase activity while ouabain demonstrates little inhibitory effect. Correspondingly, ethacrynic acid inhibits histamine release from antigen-challenged mast cells while ouabain does not. Both ATPase inhibition and histamine release inhibition by ethacrynic acid require the presence of the olefinic bond in the ethacrynic acid molecule.
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PMID:Ethacrynic acid inhibitable Ca2+ and Mg2+-activated membrane adenosine triphosphatase in rat mast cells. 7 76

1. The concentration dependence on ATP of mast cell histamine secretion in the presence of various concentrations of Mg2+ and Ca2+ confirms that the agonist form of ATP is the free form of ATP (ATP(free) not bound to divalent cations, i.e. ATP4-. It induces 50% activation at about 1.2 microM, maximal secretion at about 2.7 microM and 50% self-inhibition at about 4.4 microM. 2. The divalent cations Mg2+ and Ca2+ were used to buffer ATP(tree) in the range 1-8 microM in the presence of much higher concentrations of ATP(total). In addition to its effect as a buffer for ATP, Ca2+ is required for secretion. 3. With ATP(free) at 1 microM, the time-course of histamine secretion is characterized by a delay of about 10 min before secretion commences. With increasing concentration of ATP(free) the delay becomes shorter (less than 5 min with ATP(free) at 2 microM). 4. Secretion commences promptly on addition of Ca2+ to cells which have been pretreated with low concentrations of ATP(free) (less than 2 microM). This observation suggests that the delay normally observed represents the time taken for Ca2+ sensitivity to develop (i.e. probably the time taken for Ca2+ channels to open). 5. Late addition of Ca2+ to cells pretreated with higher concentrations of ATP(free) (greater than 2 microM) results in a reduced amount of histamine secretion compared with that which normally occurs. This reduction (which increases with time of exposure to ATP) and the self-inhibition due to higher concentrations of ATP(free) may be two facets of a common inhibitory mechanism. 6. These results are discussed in the light of other experiments which show that mast cells treated with ATP(free) at self-inhibitory concentrations become permeable to phosphorylated metabolites and nucleotides.
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PMID:Activation and inhibition of calcium-dependent histamine secretion by ATP ions applied to rat mast cells. 9 38

In the presence of Ca2+ and Mg2+, the chemotactic fragment of C5, the synthetic chemotactic oligopeptide formyl-methionyl-leucyl-phenyl-alanine, and the ionophore A23187 aggregated human neutrophils. Aggregation induced by the two chemotactic factors was transient and reversed within 2 to 4 minutes after exposure; aggregation induced by A23187 was sustained and continued to increase over 15 minutes. In the absence of the bivalent cations, none of these three agents aggregated the cells. If bivalent cations were added after cell contact with a chemotactic factor, aggregation was detected after, but not before, addition of the cations. Under these conditions, the magnitude of the aggregation response was sharply reduced: cells preincubated with a chemotactic factor for longer than 2 to 4 minutes aggregated minimally after addition of bivalent cations. Moreover, cells preincubated with a chemotactic factor for 4 minutes, exposed to bivalent cations, and then rechallenged with the same chemotactic factor also showed a minimal aggregation response, ie, the cells were "desensitized" to the original stimulus. However, cells desensitized to one of the chemotactic factors still aggregated prominently when exposed to the other chemotactic factor or to A23187. Cells could not be desensitized to the ionophore A23187. Desensitization of the neutrophil aggregation response closely resembles desensitization of mast cell and leukocyte degranulation. Degranulation and aggregation appear to be closely related cellular responses to immunologic stimuli. Both responses may reflect alterations in surface membrane permeability to bivalent cations and/or changes in surface membrane adhesiveness to other biologic membranes.
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PMID:Desensitization of the neutrophil aggregation response to chemotactic factors. 71 43

The separate catalytic roles of Zn2+ and Mg2+ and the specificity of the prenyl pyrophosphate-binding site of the rat brain protein farnesyltransferase were explored using a purified enzyme preparation. The binding of p21Hras to the enzyme was abolished by dialysis against EDTA and restored by addition of ZnCl2, as demonstrated by chemical cross-linking. The binding of the other substrate, farnesyl pyrophosphate, was independent of divalent cations, as demonstrated by gel filtration. Transfer of the enzyme-bound farnesyl group to the bound p21Hras required Mg2+. Geranylgeranyl pyrophosphate bound to the prenyl pyrophosphate-binding site with an affinity equal to that of farnesyl pyrophosphate, but the geranylgeranyl group was not transferred efficiently to p21Hras. It also was not transferred to a modified p21Hras containing COOH-terminal leucine, a protein that was shown previously to be a good substrate for a rat brain geranylgeranyltransferase. We conclude that the protein farnesyltransferase is a metalloenzyme that most likely contains Zn2+ at the peptide-binding site. It thus resembles certain metallopeptidases, including carboxypeptidase A and the angiotensin-converting enzyme. Strategies previously developed to screen for inhibitors of those enzymes may aid in the search for inhibitors of the protein farnesyltransferase.
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PMID:Divalent cation and prenyl pyrophosphate specificities of the protein farnesyltransferase from rat brain, a zinc metalloenzyme. 155 43

The neuropeptide substance P and the polyamine compound 48/80, both known to activate mast cell secretory processes, increased the rate of GTP S binding to G-proteins purified from calf brain (Go/Gi mixture). The GTPase activity of G-proteins was also increased by substance P and compound 48/80 in a dose-dependent and Mg2+-dependent way. These effects were similar to those of the wasp venom peptide mastoparan, another histamine releaser of rat peritoneal and human skin mast cells. This suggests that the secretory property of compound 48/80 and substance P is not due to a receptor-mediated process but, like mastoparan, results from a direct activation of G-proteins.
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PMID:Direct activation of GTP-binding regulatory proteins (G-proteins) by substance P and compound 48/80. 168 15

Enolase in the presence of Mg2+ catalyzes the elimination of H2O from 2-phosphoglyceric acid (PGA) to form phosphoenolpyruvate (PEP) and the reverse reaction, the hydration of PEP to PGA. The structure of the ternary complex yeast enolase-Mg2(+)-PGA/PEP has been determined by X-ray diffraction and refined by crystallographic restrained least-squares to an R = 16.9% for those data with I/sigma (I) greater than or equal to 2 to 2.2-A resolution with a good geometry of the model. The structure indicates the substrate molecule in the active site has its hydroxyl group coordinated to the Mg2+ ion. The carboxylic group interacts with the side chains of His373 and Lys396. The phosphate group is H-bonded to the guanidinium group of Arg374. A water molecule H-bonded to the carboxylic groups of Glu168 and Glu211 is located at a 2.6-A distance from carbon-2 of the substrate in the direction of its proton. We propose that this cluster functions as the base abstracting the proton in the catalytic process. The proton is probably transferred, first to the water molecule, then to Glu168, and further to the substrate hydroxyl to form a water molecule. Some analogy is apparent between the initial stages of the enolase reverse reaction, the hydration of PEP, and the proteolytic mechanism of the metallohydrolases carboxypeptidase A and thermolysin. The substrate/product binding is accompanied by large movements of loops Ser36-His43 and Ser158-Gly162. The role of these conformational changes is not clear at this time.
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PMID:Mechanism of enolase: the crystal structure of enolase-Mg2(+)-2-phosphoglycerate/phosphoenolpyruvate complex at 2.2-A resolution. 200 20

We have previously reported the presence of an ATPase, stimulated by calcium and magnesium, on the outer surface of the rat peritoneal mast cell. Experiments in which the enzyme activity was enhanced or inhibited showed a relationship to histamine secretion. Enhanced enzyme activity with increasing concentrations of the substrate (ATP) was associated with a potentiation of histamine release, and a pronounced inhibition of the enzyme caused an inhibition of the release. In the present work we have studied the influx and efflux of calcium in mast cells in relation to the activity of the Ca2+-Mg2+ ATPase on the mast cell membrane. The enzyme activity is shown to be related to calcium influx and has no effect on calcium efflux. Stimulation of the enzyme with ATP is associated with increased calcium influx into the mast cell, and inhibition of the enzyme with AMP causes inhibition of the calcium uptake. In both cases calcium efflux is unaffected. The function of the enzyme is thus different from the calcium efflux enzyme on the cytoplasmic surface, described in other cells. In addition, the Ca2+-Mg2+ ATPase on the mast cell surface is neither stimulated by calmodulin nor inhibited by the calmodulin antagonists, trifluoperazine and W-7. In mast cells the low cytosolic calcium concentration seems to be maintained by Na+-Ca2+ countertransport. Phosphorylation of the Ca2+-Mg2+ ATPase on the mast cell is likely to be associated with Ca2+ release at the cytoplasmic surface of the plasma membrane. It is thus possible that ATP hydrolysis in the membrane stimulates the contraction of microfilaments in the membrane and the cytoskeleton, and promotes the migration of the granules to the plasma membrane.
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PMID:Role of a Ca2+-Mg2+ ATPase on the mast cell surface in calcium transport and histamine secretion. 244 Feb 67

In the present study some properties of an inhibitory extract of synaptosomal membrane Na+, K+-ATPase were investigated. This extract (peak II) was prepared by gel filtration in Sephadex G-50 of a soluble fraction of the rat cerebral cortex. Ultrafiltration of peak II through Amicon membranes indicated that the inhibitor has a low MW (less than 1000). The inhibitory activity was not modified by heating in neutral pH at 95 degrees C for 20 min but it was destroyed by charring in acid pH at 200 degrees C for 120 min. The inhibitory activity decreased by incubation of peak II with carboxypeptidase A. These findings suggest that the factor responsible for the inhibition of Na+, K+-ATPase activity is probably a polypeptide. On the other hand, the inhibition was reverted by the chelators EDTA and EGTA, indicating the participation of an ionic compound as well. The increase of Mg2+ concentration during the enzyme assay did not increase the inhibition, indicating that the ion involved might not be vanadate. It is suggested that both a polypeptide and an ionic compound coparticipate in the inhibitory effect of peak II on Na+, K+-ATPase activity.
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PMID:The inhibitory activity of a brain extract on synaptosomal Na+, K+-ATPase is sensitive to carboxypeptidase A and to chelating agents. 283 64

Transitory swelling of mesenteric mast cells was observed when 24 h-fasted rats were given access to food. Atropine, an anti-muscarinic drug given (1 mg/kg, i.p.) 60 min prior to feeding, prevented this response; carbachol, a cholinomimetic drug caused it to occur when given (2 micrograms/kg, i.v., 10 min) to fasted rats. Mast cells in the mesentery excised from fasted rats, presented swelling in vitro within 1 min following exposure to 10(-7) M carbachol. This response was inhibited by atropine (10(-8) M) or hexamethonium (10(-8) M), indicating that stimulation of a parasympathetic nerve pathway, reported to exist in rat mesentery, could induce mast cell swelling. Exposure to a Ca2+ free medium also led to rapid swelling of mast cells in the mesentery excised from fasted rats. This result, as well as inhibition of the mast cell response to carbachol caused by increasing the Ca2+ (but not by increasing the Mg2+) content of the incubation medium, suggests that swelling was caused by a sudden decrease of Ca at mast cell membrane sites controlling ion/water fluxes. Mast cells swollen by feeding, carbachol or Ca-lack, reverted to their original condition within 20 min when incubated in balanced salt buffer. Such reversal did not occur in a KCl-enriched medium. An equivalent (in terms of ionic strength), increase in NaCl, did not reproduce this effect, indicating that mast cells have K+-dependent means of compensating for endogenously or drug-induced volume changes. Swelling caused by cholinergic stimulation of mast cells was not accompanied by granule exocytosis.2+ carbachol-treated rat blood in vivo or in vitro, is discussed in terms of putative mast cell-controlled, localized homeostasis in the rat mesentery.
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PMID:Atropine and hexamethonium-sensitive, Ca/K-modulated, reversible swelling of mast cells in rat mesentery, due to feeding or exposure to carbachol. 290 18


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