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J C Foreman

Publications and source records attributed to J C Foreman.

At least 91 records · Page 5Linked to original sources

Interaction of neurotensin with the substance P receptor mediating histamine release from rat mast cells and the flare in human skin.

1 Substance P induced histamine release from rat peritoneal mast cells in a dose-dependent manner over the concentration range 1 to 10 microM. 2 At concentrations in the range 2.5 to 1 0 microM, neurotensin produced only about 5% release of histamine, which was substantially less than the maximum effect obtained with substance P. 3 Neurotensin, 2.5 to 10 microM produced graded inhibition of histamine release induced by substance P. The inhibitory effect of neurotensin was not seen when histamine release was induced by an antigen-antibody effect of neurotensin was not seen when histamine release was induced by an antigen-antibody reaction or by the ionophore, A 23187. Some evidence was obtained to suggest that compound 48/80 may interact with the same receptor as substance P and neurotensin. 4 [D-Arg8]neurotensin, [D-Arg9]neurotensin, xenopsin and the C-terminal octapeptide of substance P (SP4-11) all inhibited histamine release by substance P, but physalaemin did not. 5 Neurotensin inhibited the wheal and flare reactions induced by substance P in human skin. 6 [D-Trp7,9]substance P released histamine from rat mast cells and was about 12 times more potent than substance P itself. [D-Trp7,9]SP1-11 also produced wheal and flare responses in human skin, being 1.8 times more potent than substance P in the production of flare.

Adult↗

The effects of substance P on histamine and 5-hydroxytryptamine release in the rat.

1. Substance P (SP) induces histamine release from isolated rat peritoneal mast cells at concentrations of 0.1-10 muM.2. Inhibitors of glycolysis and oxidative phosphorylation prevent the release of histamine induced by SP.3. Cells heated to 47 degrees C for 20 min release histamine when treated with an agent causing cell lysis but fail to release in response to SP.4. SP does not release histamine by interacting with cell-bound IgE.5. Histamine release by SP is rapid, with more than 90% of the response occurring within 1 min of the addition of the peptide to mast cells at 37 degrees C.6. Substance P, unlike antigen-antibody or compound 48/80, does not show enhanced release of histamine when calcium (0.1-1 mM) is present in the extracellular medium but calcium increases the response to SP when the ion is added after the peptide. Extracellular calcium (0.1-1 mM), magnesium (1-10 mM) and cobalt (0.01-0.1 mM) all inhibit SP-induced histamine release when added before the peptide. Pre-treatment of the cells with EDTA (10 mM) and washing in calcium-free medium inhibits the histamine release induced by SP.7. Histamine release induced by SP was optimum at an extracellular pH of 7.2.8. A number of peptides structurally related to SP were examined for histamine-releasing activity. At the concentrations tested, the N-terminal dipeptides Lys-Pro and Arg-Pro, tuftsin, physalaemin, eledoisin, SP(3-11), SP(4-11) and [p-Glu(6), p-amino Phe(7)]-SP(6-11) were all found to be inactive. The relative activities of the other peptides were: [Formula: see text]9. Rat basophilic leukaemia cells (RBL-2H3) fail to respond to SP at concentrations which activate rat mast cells. Release of 5-hydroxytryptamine by immunological activation of RBL cells is not changed by the presence of SP.10. The mechanism of action of SP on mast cells and the nature of the SP receptor on mast cells is discussed in relation to SP receptors in other cell types.

Animals↗

Induction of histamine secretion by polycations.

Poly(arginine), poly(lysine) and poly(ornithine) induce histamine secretion from human basophil leukocytes in the concentration range 1--100 nmol/l. Histamine secretion induced by poly(arginine) requires extracellular calcium at 0.1--1 mmol/l. Strontium (1--10 mmol/l) will substitute for calcium. Lanthanum (30--90 nmol/l) inhibits histamine release induced by poly(arginine). Histamine secretion induced by poly(arginine) is inhibited by 1--30 mumol/l N-ethyl-maleimide, 0.3--3 mmol/l 2-deoxy-D-glucose, 0.3--3 mmol/l dibutyryl cyclic AMP, 0.3--3 mmol/l, adenosine 3'5'-cyclicphosphorothioate. The action of poly(arginine) is inhibited by pretreatment of basophils at 47 degrees C or with neuraminidase. 10 microgram/ml heparin inhibits the response to poly(arginine). Histamine releasing potency of the polymer amino acids is dependent on chain length of the peptide. Succinylated poly(lysine) is inactive. Monomer amino acids do not release histamine and do not inhibit the action of the polymers. Histones and protamine do not release histamine, nor do the peptides eledoisin and tuftsin. Putrescine, cadaverine, spermine and spermidine do not release histamine. Poly(glutamic acid), poly(aspartic acid) and poly(tyrosine) are also inactive. The IgE-mediated release of histamine appears to be independent of that mediated by poly(arginine).

Amino Acids↗

Modulation of the rate of histamine release from basophils by cyclic AMP.

Rates of histamine release from human basophil leukocytes have been studied in response to three different stimuli: antigen, ionophore A23187 and strontium ions. Dibutyryl cycle AMP and other agents which are assumed to cause a rise in intracellular levels of cyclic AMP accelerate the release of histamine induced by all of the stimuli. In addition, dibutyryl cyclic AMP caused an inhibition of the maximum release obtainable with antigen stimulation but no inhibition of the maximum release obtainable with ionophore A 23187 or with strontium ions alone.

Basophils↗

Induction of calcium flux across the rat mast cell membrane by bridging IgE receptors.

Rabbit antibody against IgE receptors or its F(ab')2 fragments induced an increase of 45Ca uptake into normal mast cells, and this process was accompanied by histamine release. Evidence was obtained that a substantial portion of 45Ca uptake was due to movement of calcium across the cell membrane. Neither 45Ca uptake nor histamine release was induced by Fab' monomer fragments of the antireceptor antibody. However, bridging of receptor-bound Fab' fragments by antirabbit IgG or bridging of receptor-bound IgE by anti-IgE induced an increase in 45Ca uptake. The results collectively indicate that crosslinking IgE receptors increases the membrane permeability of the mast cells toward calcium.

Animals↗

The action of strontium on basophil leukocytes and its use to probe the relationship between immunologic stimulus and secretory response.

Strontium will substitute for calcium in the activation of histamine secretion from human basophil leukocytes stimulated by an immunologic reaction or by the ionophore A23187. Strontium is required in 10-fold higher concentration (1 to 10 mM) to activate histamine release compared with calcium (0.1 to 1.0 mM). In terms of maximum release obtainable for a particular immunologic stimulus, strontium is more effective than calcium. Results are presented to show that calcium and strontium act at the same site but strontium is a more sensitive probe for that site. Strontium can be used to demonstrate that immunologic stimuli activate calcium-binding sites in basophils even when no secretion is observed in the presence of calcium. It is suggested that the degree of secretion observed from basophils depends on the number of occupied Fc receptors for IgE and the coupling of these Fc receptors to calcium transport sites.

Basophils↗

Spontaneous histamine secretion from leukocytes in the presence of strontium.

Basophil leukocytes from human blood secrete histamine in the absence of a membrane stimulus when incubated in a medium containing Sr++, 1 to 10 mM. Spontaneous histamine secretion in the presence of Sr++ is inhibited by La+++, 1 to 1000 nM and 2 deoxy-D-glucose, 30 to 300 microM. Spontaneous secretion in the presence of Sr++ increases with increasing pH in the range 6.5 to 8.5. Agents which cause a rise of intracellular cyclic AMP level increase the spontaneous secretion in 194th presence of Sr++. The results suggest that spontaneous histamine release is a secretory response of the cells, and evidence is provided for a dual role of cyclic AMP in the control of histamine secretion.

Basophils↗

The relationship between histamine secretion and 45calcium uptake by mast cells.

1. Unstimulated mast cells from the peritoneal cavity of the rat take up (45)Ca: the initial phase of rapid uptake being complete after 1 min incubation of the cells with the isotope. Stimulation of the mast cells with an antigen-antibody reaction, dextran or concanavalin A induces an increase in the uptake of (45)Ca which is accompanied by a release of granular material: this increase in (45)Ca uptake is also complete in 1 min. The majority of the stimulated (45)Ca uptake cannot be explained in terms of binding of Ca to released granular material, or to an enlargement in either the extracellular compartment or the cell surface area.2. The magnitude of the increase in (45)Ca uptake caused by stimulating the mast cells increases when the degree of histamine secretion increases.3. The increased (45)Ca uptake induced by stimulation of the mast cells and the degree of histamine secretion are both dependent on extracellular H ion concentration. Changes of pH cause similar changes in (45)Ca uptake and secretion with maxima at pH 7.5.4. Two thirds of the (45)Ca uptake induced by an antigen-antibody reaction or by the Ca ionophore A 23187 is unaffected by inhibiting glycolysis and oxidative phosphorylation. Histamine secretion on the other hand is practically abolished by this metabolic inhibition. Thus, (45)Ca uptake proceeds in the absence of the discharge of granules.5. Dibutyryl cyclic AMP or theophylline inhibit both the increase in (45)Ca uptake and the histamine secretion caused by stimulating mast cells with an antigen-antibody reaction. Cyclic AMP, cyclic GMP and dibutyryl cyclic GMP have no effect on uptake or secretion.6. The Ca ionophore, A 23187, induces uptake of (45)Ca and histamine secretion, neither effect being inhibited by either dibutyryl cyclic AMP or theophylline.7. Phosphatidyl serine increases both (45)Ca uptake and the histamine release induced by an antigen-antibody reaction, dextran or concanavalin A.

Adenine Nucleotides↗