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F L Pearce

Publications and source records attributed to F L Pearce.

At least 127 records · Page 7Linked to original sources
PubMed1981

Inhibition of histamine secretion from mast cells.

Histamine secretion from mast cells may be inhibited by elevated intracellular levels of cyclic AMP and by several anti-allergic drugs. These compounds are claimed to act directly on the calcium-gating mechanism activated by the anaphylactic reaction, preventing influx of Ca2+ from the external environment and so blocking exocytosis. To examine this hypothesis further, we have compared here the histamine secretion induced by immunoglobulin E-directed ligands in the presence and absence of added calcium and by the ionophore A23187. Exocytosis evoked by these former agents was originally considered to be almost totally dependent on extracellular calcium but recent studies have shown otherwise. In the absence of added cation, the agents act by mobilizing membrane-bound or intracellular stores of calcium. We show that here that a variety of anti-allergic drugs are potent inhibitors in the conditions used, suggesting that alternative explanations for their action must be sought.

Animals↗
PubMed1981

Role of membrane bound calcium in histamine secretion from rat peritoneal mast cells.

Calcium loosely bound to the mast cell membrane may be utilized for histamine release induced by antigen, concanavalin A, compound 48/80 and the calcium ionophore A23187. Cells incubated in the presence of calcium and diluted into a medium free of divalent cations give a maximal release of histamine which decays with time, consistent with dissociation of the ion from the membrane. Anti-rat IgE and suboptimal concentrations of the ionophore show an immediate decrease in response followed by a further progressive decay. These results are consistent with the slower progress decay. These results are consistent with the slower time-course of secretion shown by these agonists, thus permitting dissociation of calcium from the membrane, before exocytosis is induced. In accord with this hypothesis, the initial suppression of response to the ionophore is reversed by preincubation of the cells with adenosine which enhances the rate of histamine release. The response of dextran is totally abolished by the described treatment, supporting suggesting that free extracellular calcium may be required for the polysaccharide to express its activity.

Adenosine↗
PubMed1981

Role of intra- and extracellular calcium in histamine release from rat peritoneal mast cells.

The present study provides evidence for a number of calcium pools important in histamine secretion from the mast cell. Firstly, calcium loosely bound to the cell membrane, and in rapid equilibrium with the extracellular environment, may be utilized for histamine release induced by most secretagogues. Secondly, all inducers are able to mobilize deeply buried or internal stores of calcium to initiate exocytosis. Finally, calcium bound to regulatory sites in the membrane may modulate the secretory process. Removal of calcium from the latter sites by brief treatment with chelating agents markedly enhances the secretory response in the absence of extracellular calcium, probably by facilitating the mobilization of bound stores of the ion. Saturation of these sites in the presence of excess calcium inhibits the release process and may restrict influx of the cation.

Animals↗
PubMed1981

Effect of lanthanide ions on histamine secretion from rat peritoneal mast cells.

1 Ions of the lanthanide series (lanthanum-lutetium) inhibit histamine release induced by allergen and anti-IgE in the presence of extracellular calcium. The inhibition is dose-dependent in the range 10(-6) to 10(-9) M and there is no marked difference in potency between the lanthanides. 2 The response to lanthanum is biphasic and higher concentrations (10(-4) M) potentiate the release. Maximal concentrations (10(-3) M) again abolish secretion. 3 The effect of concanavalin A is weakly antagonized by lanthanum but strongly inhibited by higher lanthanides. 4 Inhibition of histamine release evoked by basic agents is markedly dependent on the ionic radius of the lanthanide. In the presence of extracellular calcium, dysprosium is the most effective inhibitor. Similar results are observed with dextran. In the absence of calcium, there is a regular increase in inhibition with decreasing ionic radius. 5 Inhibition of release in the presence of calcium is immediate and does not require preincubation with the lanthanide. The antagonism due to lanthanum is competitive and the pA2 values vary with the secretagogue. In contrast, the inhibitory effect in the absence of extracellular calcium increase progressively with time. 6 These results are discussed in terms of the calcium-pools important in histamine release and the mode of action of different secretagogues.

Animals↗
PubMed1981

Role of a renal arginylesteropeptidase in the production of a renotrophic factor in unilaterally nephrectomized rats.

1. Renal cortical slices incubated for 4 hr in culture medium in the presence of either dibutyrylguanosine-3': 5'-cyclic monophosphate (dibutyryl cyclic GMP, 10(-6)m) or freeze-dried normal rat plasma (35 mug mg(-1) wet wt. tissue) did not show any change in dry weight or protein content. However, addition of freeze-dried normal plasma together with dibutyryl cyclic GMP led to an increase in both parameters.2. Unilateral nephrectomy produced a marked increase in the level of arginylesteropeptidase in the renal cortex of the remaining kidney. A similar increase was observed in renal cortical slices incubated with dibutyryl cyclic GMP in vitro.3. The renal cortical esteropeptidase was inhibited by phenylmethylsulphonyl fluoride (PMSF, 2 mm). The inhibitor did not, however, prevent the normal increase of dry weight and protein content of renal cortical slices incubated with plasma from unilaterally nephrectomized rats. Similarly, control normal plasma incubated with cortical slices from a kidney removed 10 min after unilateral nephrectomy became endowed with renotrophic activity (Dicker & Morris, 1980b) but this activation was abolished by PMSF.4. Control plasma treated with a purified arginylesteropeptidase and incubated for 4 hr with renal cortical slices produced a hypertrophy of the slices similar to that evoked by plasma from a unilaterally nephrectomized rat.5. Since following unilateral nephrectomy there is a rapid increase in the level of cyclic GMP in the renal cortical tissue of the remaining kidney (Dicker & Greenbaum, 1977) it is suggested that this increase leads to the induction of a specific arginylesteropeptidase. The possibility that the enzyme then cleaves a renotrophic precursor normally present in the plasma, so converting it to an active form, is discussed.

Aminopeptidases↗
PubMed1981

Characteristics of and calcium requirements for histamine release from rat peritoneal mast cells treated with concanavalin A.

Concanavalin A (Con A) produced a selective release of histamine from rat peritoneal mast cells in the presence and absence of added calcium. Secretion under both conditions was enhanced by adenosine, but only the former release was potentiated by phosphatidyl serine (PS). The latter release was abolished by depletion of intracellular reservoirs of calcium and probably reflected mobilization of these stores. A brief exposure to chelating agents enhanced the response to Con A whereas supramaximal concentration of calcium depressed the response. This result suggests that superficial calcium-stores in the membrane may regulate movement of the cation into the cytosol. The activated state induced by Con A and PS was particularly stable and did not decay with time over a 30 min period. The kinetics of the release process were independent of added calcium, indicating that calcium-translocation is not the rate-limiting step in the exocytotic mechanism.

Adenosine↗
PubMed1981

Effect of anti-allergic compounds on histamine release from rat peritoneal mast cells treated with concanavalin A.

The anti-allergic drugs theophylline, doxantrazole, quercetin, dibutyryl cyclic AMP, and disodium cromoglycate prevented histamine release induced by concanavalin A in both the presence and absence of extracellular calcium. The compounds were generally most effective in the absence of added calcium and least effective in the simultaneous presence of calcium and phosphatidyl serine. The activity of the test drugs in calcium-free media clearly cannot be explained in terms of their postulated ability to block movement of the ion from the external environment into the cell. Alternative modes of action are thus considered.

Animals↗
PubMed1980

Differential reactivity of isolated mast cells from the rat and guinea pig.

The effects of various chemical histamine liberators on isolated rat peritoneal, rat mesenteric and guinea-pig mesenteric mast cells were examined. All three cell types responded, but to different degrees, to calcium ionophores and surface active agents. The rat mesenteric cells also reponded, but less effectively than the peritoneal cells, to compound 48/80, peptide 401 from bee venom and ATP. Rat mesenteric cells were essentially refractory to the action of dextran and guinea-pig cells were almost totally unresponsive to the named secretagogues. These results show that there are marked functional differences between the mast cells examined and suggest that isolated tissue cells may usefuly complement rat peritoneal cells in the study of anaphylactic and anaphylactoid reactions.

Adenosine Triphosphate↗
PubMed1980

Inhibition of histamine release induced by compound 48/80 and peptide 401 in the presence and absence of calcium. Implications for the mode of action of anti-allergic compounds.

Histamine may be released from rat peritoneal mast cells by compound 48/80 and peptide 401 in the presence and absence of extracellular calcium. The process is non-cytolytic and requires an intact cell metabolism. The release produced under both conditions is inhibited by disodium cromoglycate, theophylline, dibutyryl cyclic AMP and (at high concentrations) quercetin. The efficacy of the drugs in the absence of extracellular calcium cannot be explained in terms of their postulated effect on the calcium-gating mechanism operative in anaphylactic secretion. Alternative modes of action of the compounds are thus considered.

Animals↗
PubMed1980

Some studies on the release of histamine from mast cells stimulated with polylysine.

1 Polylysine is an extremely potent releaser of histamine from rat peritoneal mast cells. Isolated mesenteric mast cells of the rat also respond to the secretagogue but guinea-pig mesenteric cells are unreactive. 2 The release does not require the presence of extracellular calcium ions but shows some dependence on internal stores of the cation. 3 The effect of polylysine is blocked by extremes of temperature and by metabolic inhibitors. 4 The release is very rapid and is virtually complete within 10 s of adding the inducer. 5 The release is unaffected by the anti-allergic drug, doxantrazole, but is inhibited by theophylline and disodium cromoglycate. The latter compounds are effective in both the presence and absence of added calcium. This result is discussed in terms of the postulated effect of the drugs on calcium transport.

Animals↗
PubMed1980

Calcium pools involved in histamine release from rat mast cells.

Basic secretagogues, antigen, concanavalin A, the ionophore A23187 and, to a lesser extent, anti-rat IgE produce a significant release of histamine from rat peritoneal mast cells in the absence of extracellular calcium. This release is due to the mobilization of intracellular reservoirs of calcium. The release is abolished by prolonged exposure to chelating agents, but is potentiated by brief exposure to these substances. It is suggested that the latter treatment removes calcium from a superficial, regulatory site and thus facilitates the mobilization of more internal pools of the ion. By analogy with smooth muscle, these regulatory sites may also modulate calcium influx into the cell. On the basis of these and other results, the possible calcium pools important in histamine secretion are discussed.

Animals↗