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 second order rate constant, k2, for the inhibition of mast cell protease I by phenylmethanesulfonyl fluoride (PMSF) is lower for intact mast cells and isolated granules with intact membranes than for granules stripped of their membranes and suspended in medium at pH 7.1. In order to test the hypothesis that the decreased activity of the protease in intact granules is attributable to low pH, two agents capable of lowering pH in intracellular compartments similar to mast cell granules were tested. Ammonium chloride increased k2 of the protease in isolated granules with intact membranes and mast cells and wash out of the salt partially reversed this effect. Treatment of cells with nigericin also substantially increased the rate of protease inactivation by PMSF. These results are consistent with the proposal that the observed k2 is determined in whole or part by a low pH of the granule in situ or isolated with intact membranes. If the low k2 in situ is solely dependent on low pH, then the rate of protease inhibition can be utilized as an endogenous probe of granule pH. On this basis we have estimated the pH of the intracellular granule as 5.2 and that of the isolated granule with its membrane intact as 6.0. The value for the pH of granules in situ is lower than that previously estimated, and we have considered possible bases for this discrepancy.
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PMID:Evidence for control of mast cell granule protease in situ by low pH. 634 Oct 76

A human mast cell line (HMC-1) has been used to study the effect of cytosolic alkaline pH in exocytosis. Compound 48/80, concanavalin A, and thapsigargin do not induce histamine release in HMC-1 cells. Although thapsigargin does not activate histamine release, it does show a large increase in cytosolic Ca(2+), and no change in cytosolic pH. However, when HMC-1 cells were activated with ionomycin, a significant histamine release takes place, and this effect is higher in the presence of thapsigargin. Both drugs show an additive effect on cytosolic Ca(2+) levels. Ammonium chloride (NH(4)Cl) does activate cytosolic alkalinization and histamine release, with no increase in cytosolic Ca(2+). NH(4)Cl does block the release of internal Ca(2+) by thapsigargin, not by ionomycin, and decreases Ca(2+) influx stimulated by these drugs. Under conditions in which the alkalinization induced by NH(4)Cl is blocked by acidification with sodium propionate, histamine release is inhibited. The release of histamine is also observed when NH(4)Cl is added after propionate addition, regardless of the final pH value attained. Our results show that a shift in pH alkaline values, even with final pH below 7.2 is enough to activate histamine release. A shift to less acidic values is a sufficient signal to activate the cells.
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PMID:Mast cell exocytosis can be triggered by ammonium chloride with just a cytosolic alkalinization and no calcium increase. 1575 34