PubMed Health⌕ Search

Biomedical subjects

F L Pearce

Publications and source records attributed to F L Pearce.

At least 91 records · Page 5Linked to original sources
PubMed1984

Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells.

Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis. This contrasts with our previous observation that cromoglycate is inactive in this system. The present effect is immediate and does not decrease on preincubation with the drug. The flavonoids acacetin , apigenin , chrysin , and phloretin also demonstrate significant activity but are less potent than quercetin. Catechin, flavone, morin, and taxifolin are inactive. These results resemble those previously reported for the human basophil. In contrast, all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC. Acacetin and chrysin are the most effective inhibitors and are more active than quercetin. Rutin (the glycane of quercetin) and phlorezin (the glycane of phloretin) are inactive in both systems. These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC.

Animals↗
PubMed1984

A comparison of histamine secretion from peritoneal mast cells of the rat and hamster.

Functional mast cells have been obtained by peritoneal lavage of the rat and hamster. Both cell types released histamine on stimulation with appropriate dilutions of anti-rat IgE and anti-hamster serum. The maximum response evoked by each reagent was significantly greater for the hamster cells. The release was non-cytotoxic and was in each case blocked by the corresponding soluble antigen. The rat and hamster cells responded to concanavalin A and the lectin from lentil. Phosphatidylserine (PS) potentiated the release only from the rat cells. In the absence of the lipid, the hamster cells were more reactive. The lectin from wheat germ, in the presence of PS, evoked histamine secretion only from the rat cells. Both populations were refractory to the lectin from soybean and to protein A. Rat peritoneal cells were more responsive to the basic secretagogues compound 48/80 and peptide 401 (the MCD-peptide from bee venom). These differences were less marked in the case of polylysine and polyarginine. The two cell populations responded to the calcium ionophores A23187, ionomycin and chlortetracycline. The hamster cells were significantly more sensitive to the former two liberators but markedly less reactive to chlortetracycline. Adenosine 5'-triphosphate (ATP) and dextran were potent histamine liberators from the rat cells but were totally ineffective against the hamster. Acetylcholine and carbamylcholine had no effect on either cell type. These results are discussed in terms of the functional heterogeneity of mast cells from different sources.

Animals↗
PubMed1983

Use of chlortetracycline to monitor calcium mobilization during histamine secretion from the mast cell: a cautionary note.

Purified rat peritoneal mast cells incubated with chlortetracycline showed a fluorescence emission spectrum characteristic of the membrane-bound complex with calcium ions. Treatment of the cells with chelating agents, which are thought to deplete the mast cell of sequestered calcium, led to a marked reduction in fluorescence. Activation of the cells with a number of secretagogues produced an abrupt fall in fluorescence emission, indicative of the release of bound calcium, and an accompanying liberation of histamine. These changes were, however, blocked by metabolic inhibitors and anti-anaphylactic agents, suggesting that they occurred subsequently to the exocytotic process. The significance of these findings in the application of the method to other systems is discussed.

Animals↗
PubMed1983

Dispersed sensory ganglion cells cleave an active entity from nerve growth factor coupled to Sepharose.

Dispersed sensory ganglion cells from the embryonic chick, but not cells from other tissues, liberate biologically active material from nerve growth factor coupled to Sepharose beads. Experiments with such insolubilized material cannot then be taken as evidence for the existence of an external membrane receptor for the factor and may indicate that responsive cells have the ability to cleave an active fragment from the polypeptide.

Animals↗
PubMed1983

Histamine secretion from mast cells treated with chlortetracycline (aureomycin): a novel calcium ionophore.

The novel calcium ionophore chlortetracycline (CTC) induced histamine secretion (less than or equal to 90%) from isolated rat peritoneal mast cells in a pH and dose-dependent fashion. The process was dependent on exogenous calcium ions and was inhibited by extremes of temperature and metabolic blockers. The release was rapid, being essentially complete within 1 min, but the half-life of the process varied inversely with the concentration of the ionophore. In contrast to receptor-mediated ligands, but in keeping with other ionophores, the activated state induced by CTC did not decay with time. The secretion was effectively inhibited, according to the concentration of the ionophore, by disodium cromoglycate and other anti-allergic or cyclic AMP-active drugs. These results confirm our previous contention that these agents do not act on receptor-mediated calcium-channels. CTC induced a significant (less than or equal to 50%) release of histamine from enzymically dispersed rat mesenteric mast cells but was essentially inactive against isolated mast cells from the mesentery or lung of the guinea-pig. These results extend our former observations on the functional heterogeneity of mast cells and show that, in common with other secretagogues, ionophores may exhibit selectivity in their mode of action.

Animals↗
PubMed1983

Mast cells isolated from guinea-pig lung: characterization and studies on histamine secretion.

A method has been developed for the dispersion of guinea-pig lung into its component cells using the proteolytic enzyme collagenase. The procedure typically yielded 5 X 10(6) mast cells per g of tissue with a recovery of histamine of ca. 20%. The mast cells comprised 2% of the total nucleated cells, had a histamine content of 1-2 pg per cell and exhibited a low spontaneous release of the amine (ca. 6%). In contrast to the rat peritoneal mast cell, guinea-pig lung mast cells were refractory to the action of compound 48/80, peptide 401 (MCD-peptide), dextran and Concanavalin A. However, the cells released histamine on antigenic challenge following active sensitization and dose-dependent histamine secretion was also produced by the ionophores A23187, ionomycin and Br-X537A. These results further emphasize the functional heterogeneity of mast cells obtained from different species and tissues.

Animals↗
PubMed1983

Calcium antagonists and histamine secretion from rat peritoneal mast cells.

The calcium antagonists verapamil and nifedipine inhibited histamine release induced from rat peritoneal mast cells by a number of secretory stimuli. However, the concentrations required were much higher than those active in smooth muscle preparations. The inhibition was unaffected by elevated levels of external calcium and the drugs prevented release in the absence of added calcium. The novel calcium antagonist, PY 108-068, had no effect on histamine secretion from mast cells. These results suggest that calcium channels in the mastocyte may differ from those in smooth muscle and that at concentrations required to inhibit secretion, verapamil and nifedipine may have non-specific stabilizing effects on the mast cell membrane.

Animals↗
PubMed1983

Inhibition by disodium cromoglycate of anaphylactic histamine secretion from rat peritoneal mast cells in the presence of phosphatidylserine.

The lipid phosphatidylserine (PS) markedly potentiated anaphylactic histamine secretion from isolated rat peritoneal mast cells in the presence of extracellular calcium ions. The compound correspondingly reduced the inhibitory effect of disodium cromoglycate on the secretion induced by optimal concentrations of antigen. However, at a constant concentration of PS, suboptimal amounts of antigen were effectively inhibited by the drug. The inhibitory power of cromoglycate increased as the concentration of antigen was decreased and the corresponding control release of histamine declined. At control values similar to those observed without addition of PS, the drug inhibited secretion to a similar extent as in the absence of the lipid. At given concentrations of PS and antigen, the potency of the drug increased with decreasing degrees of sensitization of the experimental animals. These effects are not likely to reflect a direct interaction between the drug and PS since increasing the concentration of the lipid by one hundred-fold did not affect the inhibitory effect of the chromone. Further, the latter was essentially equiactive in the presence and absence of PS in calcium-free media, conditions under which the lipid did not enhance histamine release. These results are discussed in terms of the proposed modes of action of PS and cromoglycate.

Anaphylaxis↗
PubMed1983

Effect of anti-allergic and cyclic AMP-active drugs on histamine secretion from rat mast cells treated with the novel calcium ionophore chlortetracycline.

The anti-allergic drugs disodium cromoglycate, doxantrazole and quercetin, and a number of compounds known to elevate intracellular levels of cyclic AMP, inhibited histamine secretion from rat peritoneal mast cells stimulated with the novel calcium ionophore, chlortetracycline. The potency of the compounds varied inversely with the concentration of ionophore. The activity of the drugs cannot be explained in terms of their postulated effect on the receptor-mediated activation of calcium channels in the mast cell membrane. Alternative mechanisms for their action are thus considered.

Animals↗
PubMed1983

A comparison of histamine secretion from isolated peritoneal mast cells of the mouse and rat.

The effect of different histamine liberators on isolated peritoneal mast cells of the mouse and rat has been examined. Both cell types responded to the lectin, concanavalin A, and the release was in each case potentiated by phosphatidylserine. The rat cells released histamine on treatment with dextran but the mouse cells were essentially refractory to the polysaccharide. The mouse cells were significantly more responsive to the actions of the ionophore A23187 and adenosine 5'-triphosphate but much less reactive towards the polycations, compound 48/80 and peptide 401 (the MCD-peptide from bee venom). The reactivity of the mouse cells towards the latter two agents was enhanced in the absence of extracellular calcium. These results further emphasize the functional heterogeneity of mast cells from different sources.

Adenosine Triphosphate↗
PubMed1982

Characterization of chlortetracycline (aureomycin) as a calcium ionophore.

The antibiotic chlortetracycline (aureomycin) is shown to be a potent and specific calcium ionophore. The molecule extracts calcium from an aqueous environment into a bulk organic phase in a pH-dependent manner and with a stoichiometry indicative of a 1:1 complex. The antibiotic has little affinity for other alkaline earth ions or alkali metal ions in this system. The ionophore transports calcium from one aqueous phase to another across an organic solvent barrier and induces a flux of calcium into multilamellar vesicles. The potential use of the compound in examining the role of calcium in the modulation of cellular function is discussed.

Calcium↗
PubMed1982

Effect of disodium cromoglycate and cyclic AMP-active drugs on cytotoxic histamine release from rat mast cells.

Disodium cromoglycate and compounds which elevated levels of cyclic AMP in the mast cell variously inhibited cytotoxic histamine release induced by the surface active agents melittin, Tween 20 and Triton X-100. These results are inconsistent with the postulated effects of the drugs on receptor mediated calcium channels and alternative explanations of their action are considered.

Animals↗
PubMed1982

Unique functional characteristics of mucosal mast cells.

Mast cells have been isolated from the intestine (IMC) of rats previously infected with the nematode, Nippostrongylus brasiliensis. Functional studies on IMC have shown that they are responsive to antigen and possess surface IgE but, in contrast to peritoneal mast cells (PMC), IMC are unresponsive to the basic secretagogues, 48/80 and bee venom peptide 401, and hyporesponsive to ionophores. Furthermore, sodium cromoglycate, AH9679 and theophylline inhibited secretion by PMC but not IMC, whereas doxantrazole inhibited secretion by both cells. Histochemical investigations established that there is mast cell heterogeneity in the human intestine as well as in the rat. Since GALT and BALT are important in intestinal mastocytosis it is important to determine whether the distinct functional properties of IMC reflect a distinct precursor population, inducer cell, or other factors in GALT or BALT.

Animals↗
PubMed1982

Isolation and properties of mast cells from the small bowel lamina propria of the rat.

A method is described for the isolation of mast cells from the mucosa of the small intestine of rats infected with the nematode Nippostrongylus brasiliensis. The cells release histamine on challenge with IgE-directed ligands and calcium ionophores but, in contrast to rat peritoneal mast cells, are refractory to the action of basic secretagogues. The mucosal and peritoneal cells also differ markedly in their sensitivity to particular anti-allergic drugs. These results further emphasize the functional heterogeneity of mast cells from different sources.

Anaphylaxis↗
PubMed1982

A comparative study of histamine secretion from rat peritoneal and pleural mast cells.

The effects of various histamine liberators and inhibitors on isolated rat peritoneal and pleural mast cells have been compared. The pleural cells showed an increased reactivity to challenge with antigen following passive, but not active, sensitization and were more responsive to challenge with anti-IgE. Phosphatidyl serine enhanced the secretion from both cell types. Peritoneal and pleural cells exhibited virtually identical responses after treatment with chemical secretagogues in the presence of exogenous calcium, but the peritoneal cells were significantly more reactive to stimulation with basic inducers in the absence of the cation. Anaphylactic histamine secretion was comparably inhibited by a number of anti-allergic drugs but the peritoneal cells were rather more sensitive to inhibition by dibutyryl cyclic AMP. These results are discussed in terms of the general functional heterogeneity of mast cells from different sources.

Anaphylaxis↗
PubMed1982

Effect of ketotifen and oxatomide on histamine secretion from mast cells.

The anti-histaminic drugs ketotifen and oxatomide have a dual effect on rat peritoneal mast cells. At high concentrations they induce histamine release, whereas at low concentrations they inhibit secretion evoked by IgE-directed ligands. The latter effect is observed in the presence and absence of exogenous calcium. The significance of this result for the general mode of action of anti-anaphylactic drugs is discussed. Neither compound liberates histamine from isolated mesenteric cells from the rat or guinea pig, further emphasizing the functional heterogeneity of mast cells from different sources.

Animals↗