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Biomedical subjects

F L Pearce

Publications and source records attributed to F L Pearce.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1982

Phosphatidic acid induces histamine secretion from rat peritoneal mast cells.

Phosphatidic acid produces a selective, dose-dependent release of histamine from rat peritoneal mast cells. The effect is independent of exogenous calcium and probably reflects mobilization of sequestered stores of the cation. The significance of these results is discussed in terms of the possible changes in membrane lipid metabolism involved in mast cell activation.

Animals↗
PubMed1982

Some characteristics of histamine secretion from mast cells treated with ionomycin.

The ionophorous antibiotic ionomycin released histamine from rat peritoneal mast cells in both the presence and absence of added calcium ions. The response under the latter conditions was potentiated by brief pretreatment of the cells with chelating agents. The interaction between the ionophore and exogenous calcium was complex. Supramaximal concentrations of calcium potentiated the release induced by low levels of ionomycin but markedly inhibited the secretion evoked by larger amounts of the compound. Dispersed mesenteric mast cells of the rat and guinea pig also responded to ionomycin but were less reactive than the peritoneal cells.

Animals↗
PubMed1982

Mucosal mast cells. I. Isolation and functional characteristics of rat intestinal mast cells.

We have developed a procedure for the dispersion of mast cells from the intestinal lamina propria (LP) and epithelium of rats infected with the intestinal nematode, Nippostrongylus brasiliensis. The dispersed cells are morphologically and histochemically similar to intestinal mucosal mast cells (MMC) in situ and are distinguishable from peritoneal mast cells (PMC). MMC derived from the LP or epithelium of parasitized animals secrete histamine in response to the specific parasite antigens as well as anti-IgE. Unlike PMC, these cells are unresponsive to the basic secretagogues 48/80 and bee venom peptide 401. Similarly, bee venom peptide 401 conjugated with dansyl chloride binds to PMC and mast cells in the thymus and intestinal serosa, but not to mast cells in or derived from the intestinal LP and epithelium. Studies on PMC treated by the intestinal cell isolation procedure show that the functional characteristics of the MMC cannot be solely attributed to the isolation procedure. Thus, MMC have been isolated and shown to be morphologically, histochemically, and functionally different from PMC, as suggested by previous in vivo studies of the normal intestine.

Animals↗
PubMed1982

Mucosal mast cells. II. Effects of anti-allergic compounds on histamine secretion by isolated intestinal mast cells.

Functional mast cells have been isolated from the lamina propria of the small intestine of rats infected with the nematode Nippostrongylus brasiliensis. The cells released histamine on challenge with specific antigen, anti-rat IgE, concanavalin A, and calcium ionophores but were less responsive than peritoneal mast cells (MMC) from the same animals. Intestinal mucosa mast cells (PMC) were refractory to the action of the basic secretagogues peptide 401 from bee venom and compound 48/80. The anti-allergic compounds disodium cromoglycate (less than or equal to 10(-3) M), AH 9679 (less than or equal to 10(-4) M), and theophylline (less than or equal to 10(-2)) did not inhibit antigen-induced histamine secretion by MMC, although these compounds were effective against PMC. In contrast, doxantrazole (10(-5) to 10(-3) M) inhibited the secretion of histamine from both MMC and PMC in a comparable dose-dependent fashion. Thus, we have established that mast cells from different sites are functionally heterogeneous not only in their response to various stimuli for histamine secretion, but also in their responses to different pharmacologic modulators of secretion. It cannot be assumed that anti-allergic compounds effective against mast cells in one tissue site or organ will be equally efficacious against mast cells in other sites. The extent of this functional heterogeneity must be established, and its investigation may provide new insights into the biochemical events involved in mast cell secretion.

Animals↗
PubMed1982

Characteristics of histamine secretion from rat peritoneal mast cells sensitized to the nematode Nippostrongylus brasiliensis.

Peritoneal mast cells from rats immunized with the nematode Nippostrongylus brasiliensis released histamine on challenge with antigen in both the presence and absence of added calcium. The response under the latter conditions was abolished by depletion of sequestered stores of the cation and probably reflected mobilization of these stores. The release was potentiated by brief pretreatment with chelating agents and inhibited (in the absence of phosphatidyl serine, PS) by supramaximal concentrations of calcium. Calcium bound to superficial sites in the membrane may then regulate the secretory process. Histamine release in both the presence and absence of calcium was enhanced by adenosine. Only the former response was potentiated by PS, in keeping with the view that the lipid promotes influx of the cation from the extracellular environment. The activated state induced by antigen decayed with time but PS slowed this process. Histamine secretion in the absence of calcium was more rapid than in the presence of the cation, consistent with the release of bound calcium in a pulse of short duration.

Adenosine↗
PubMed1982

Effect of anti-allergic compounds on anaphylactic histamine secretion from rat peritoneal mast cells in the presence and absence of exogenous calcium.

The anti-allergic drugs theophylline, doxantrazole, quercetin, 8-bromo cyclic AMP, and disodium cromoglycate prevented anaphylactic histamine release from rat peritoneal mast cells in both the presence and absence of extracellular calcium. The activity of the test compounds under the latter conditions cannot be simply explained in terms of their postulated ability to block movement of the cation from the external environment into the cell. Alternative modes of action are thus considered.

8-Bromo Cyclic Adenosine Monophosphate↗
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↗