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Biomedical subjects

F L Pearce

Publications and source records attributed to F L Pearce.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1979

The effect of alkaline earth cations on the release of histamine from rat peritoneal mast cells treated with compound 48/80 and peptide 401.

1 Extracellular calcium ions have a dual effect on the release of histamine from rat peritoneal mast cells treated with compound 48/80 and peptide 401. The release is either potentiated or inhibited according to the relative concentrations of ion and inducer.2 Strontium similarly potentiates the release produced by optimal concentrations of inducer but higher concentrations are required than in the case of calcium. Strontium is markedly less inhibitory than calcium.3 Mast cells may be depleted of intracellular calcium by incubation for short periods with the chelating agent, ethylenediamine tetraacetic acid (EDTA). They thereby become unresponsive to compound 48/80 and peptide 401 unless calcium is reintroduced into the incubation medium. Strontium and barium, but not magnesium, will substitute for calcium in this system. Barium additionally produces a marked release of histamine even in the absence of inducer. Pretreatment with the ionophore A23187 similarly inhibits the subsequent response to peptide 401 in divalent cation-free medium. This inhibition is reversed on the reintroduction of calcium.4 Compound 48/80 and peptide 401 release histamine from mast cells incubated in isotonic sucrose in the complete absence of added metal ions. However, the corrected release under these conditions is potentiated by both mono and divalent cations.5 On the basis of these results, the possible mechanism of action of the basic releasing agents and their usefulness as models for studying histamine secretion is discussed.

Animals↗
PubMed1979

Effect of cyclic AMP on histamine release induced by compound 48/80.

Bu2 cAMP(N6, O2'-dibutyryl adenosine-3',5'-cyclic monophosphate) inhibited the response of rat peritoneal mast cells to compound 48/80 in the presence of calcium ions. In the absence of calcium, the nucleotide partially prevented the desensitization induced by chelating agents. The response of cells, allowed to accumulate Bu2 cAMP in the presence of calcium (to avoid depletion of intracellular stores of the ion) and then challenged in the absence of extracellular calcium, was also inhibited. These results are discussed in terms of the postulated effects of Bu2 cAMP on the calcium-gatubg mechanism operative in histamine secretion.

Animals↗
PubMed1978

On the mechanism of immunosympathectomy.

The effects in vivo and in vitro of the antiserum to mouse nerve growth factor (NGF) are independent of the presence of complement. These results are consistent with the view that the antiserum acts by neutralizing endogenous NGF.

Animals↗
PubMed1978

Studies on the release of histamine from isolated guinea pig mast cells stimulated by ionophore A23187 or by the anaphylactic reaction.

The divalent cation ionophore A23187 was found to produce a dose-dependent release of histamine from isolated mesenteric mast cells of the guinea pig. The process showed a specific requirement for calcium ions and was blocked by inhibitors of glycolysis. The effect of cAMP, theophylline, sympathomimetic amines and DSCG on the histamine release induced by the ionophore or by the antigen-antibody reaction was compared. In both cases, the release was inhibited by Bu2cAMP and by theophylline but higher concentrations were required with the ionophore. Adrenaline, isoprenaline and DSCG were effective only in the anaphylactic system. These results are compared with those previously reported for human leucocytes and rat peritoneal mast cells in which the release produced by the ionophore was found not to be inhibited by cAMP and its analogues. On the basis of these findings, the possible role of cAMP in the modulation of histamine release is discussed.

Anaphylaxis↗
PubMed1977

Immunogenic contaminants in mouse nerve-growth factor.

Experiments are described that confirm the presence of gamma-globulin in standard preparations of mouse nerve growth factor (7-S complex and beta subunit) and show that antibodies to this protein are present in horse antisera to the growth factor. These antibodies may be partially removed by adsorption with soluble antigen and totally removed by affinity chromatography on columns of insolubilised antigen. These procedures do not affect the potency of the antiserum in vitro or in vivo. Contaminating globulin may be removed from samples of the isolated beta subunit by gel filtration to give an immunochemically pure preparation which will permit more meaningful studies on nerve growth factor and its antiserum.

Animals↗
PubMed1977

Isolation and study of functional mast cells from lung and mesentery of the guinea pig.

A method is described for the dissociation of guinea pig lung and mesentery into their component cells. The method comprises incubation of the tissues with the enzyme pronase in Ca++- and Mg++-free saline followed by mechanical dispersion and yields on average 3-8% free mast cells. These cells are morphologically intact and viable. They retain an active sensitization or can be passively sensitized. The levels of cAMP and cGMP in the whole cell suspension respond to catecholamine, histamine or cholinergic stimulation in a way similar to that observed in the corresponding undispersed tissue. Although the separation of guinea pig mast cells from other cells proved to be more difficult than the purification of rat mast cells, an inrichment of greater than 50% has been achieved. The mast cells isolated by this method proliferate in vitro and have been cultured successfully for several months.

Anaphylaxis↗
PubMed1977

The use of porous plastic filters in the preparation of cell suspensions.

Suspensions of cells were prepared by dissociation of various tissues with the proteolytic enzyme pronase. Debris, undisrupted tissue and cell clumps were effectively removed from the suspensions by passage through VYON F porous plastic filters whereas isolated cells were recovered without significant losses. The viability of the cells, as judged by dye exclusion and subsequent behavior in tissue culture, was not affected by the treatment.

Animals↗