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J C Foreman

Publications and source records attributed to J C Foreman.

At least 73 records · Page 4Linked to original sources
PubMed1986

Characteristics of histamine release from rat mast cells in relation to the valency of the stimulating ligand.

The relationship between the valency of a ligand and the subsequent characteristics of histamine release was investigated in rat peritoneal mast cells. The cells were passively sensitized to the DNP hapten and a series of DNP-human serum albumin conjugates of known valency were used to induce histamine release. The rate of release of histamine induced by these conjugates was independent of the DNP/HSA ratio when the ratio was between 71.3 and 7.2. Marked slowing of the release occurred as the ratio was reduced below 7.2. The rate of desensitization of the cells slowed as a continuous function as the DNP/HSA ratio was reduced. 45Calcium uptake measurements showed that the changes in histamine release were paralleled by changes in the membrane permeability to calcium. The rate of release of histamine from mast cells and the rate of desensitization of the cells are discussed in terms of the size of IgE receptor complexes on the cell membrane.

Animals↗
PubMed1985

Histamine release induced by histone and phorbol ester from rat peritoneal mast cells.

Histone 10 to 50 micrograms/ml released histamine from rat peritoneal mast cells in the absence of extracellular calcium. Extracellular calcium, 1 mM produced a slight shift of the histone dose-response curve to the right. In the absence of extracellular calcium, the histamine release-response to combined stimulation with histone and substance P was saturable. Neither histone nor substance P elicited any further response when one of these agonists alone was already eliciting a maximum response, although the cells were capable of a greater degree of histamine release in the presence of compound 48/80. In the presence of extracellular calcium, substance P at a concentration not by itself producing a response, acted synergistically with histone to induce histamine release. The substance P antagonist, SP-A, inhibited histamine release by histone. The phorbol ester, TPA, released histamine in a dose-dependent manner and this response was inhibited by SP-A. It is suggested that substance P and histone interact with a common site to release histamine and the role of protein kinase C in this release mechanism is discussed.

Animals↗
PubMed1985

On the actions of substance P, somatostatin, and vasoactive intestinal polypeptide on rat peritoneal mast cells and in human skin.

Substance P (SP), somatostatin (Som), and vasoactive intestinal polypeptide (VIP) induced a concentration-dependent release of histamine from isolated rat peritoneal mast cells. The release of histamine induced by these neuropeptides was inhibited by preincubation of the cells with the SP analogue [D-Pro4,D-Trp7,9,10]-SP4-11 (SP-A) (10 microM), and also by benzalkonium chloride (10 microM). In addition, SP-A inhibited histamine release induced by compound 48/80, whilst that induced by goat anti-(rat-IgE) was unaffected. In human skin, intradermal injection of SP, Som, or VIP produced flare and wheal responses. The flares to all three peptides were inhibited by preinjection of the skin with SP-A (25 pmol), whilst the wheal responses were unaffected. It is concluded that the receptors mediating histamine release and the flare response are similar, and that SP, Som, and VIP are acting at a similar receptor to produce these effects. It is probable that this receptor is also the site of action of compound 48/80.

Animals↗
PubMed1985

Rat mast cell activation and inactivation: differences when various ligands are used to induce secretion.

The relationship between rat peritoneal mast cell activation and inactivation (desensitization) was studied for a variety of stimuli acting via IgE and IgG receptors on the cell surface. Anti-IgE, antigen (ovalbumin), anti-IgG1, anti-IgG2a and dimers, trimers and higher oligomers of IgE were used to induce histamine release from rat mast cells. All produced similar characteristics of cell activation, with a rapid rate of histamine release from the cells, release being 90% complete within 5 minutes and with calculated doubling times between 21.6 +/- 3.6 s (+/- SEM) for ovalbumin and 93.0 +/- 18.6 s (+/- SEM) for anti-IgG1. The characteristics of inactivation, however, varied with the releasing agent used. Of all the stimuli used only ovalbumin showed a rapid rate of desensitization (t 1/2 = 330 +/- 34.8 s) which correlated with the cessation of histamine release. The other stimuli showed slow rates of desensitization (t 1/2 between 1068 +/- 40.2 s for dimer and 3576 +/- 660 s for anti-IgE) even though the rate of release was rapid. Thus, although these stimuli are thought to be stimulating the cells by cross-linking of either IgE or IgG receptors, the difference in subsequent response of the cells would indicate that the transduction mechanism bringing about release can distinguish between these various stimuli. Also, it seems that the idea that duration of histamine release is determined by the rate of desensitization may need revising as with most of these stimuli, release has terminated when the cells are still in a fully activated state.

Animals↗
PubMed1985

A study of the histamine H2-receptor mediating relaxation of the parenchymal lung strip preparation of the guinea-pig.

The relaxation produced by several H2-receptor agonists and forskolin was investigated on strips of guinea-pig lung parenchyma. Dimparit, 1 microM to 10 mM, 4-methyl histamine, 0.5 microM to 100 microM and impromidine, 10 nM to 1 microM, had no effect on the tone of the unstimulated strips of lung parenchyma but caused a dose-dependent relaxation of strips that were contracted by 2-pyridylethylamine (2-PEA), 15 microM. Forskolin, 10 nM to 4 microM, produced a dose-dependent relaxation of both the stimulated and unstimulated lung strips. The muscarinic antagonist atropine, 1 microM, and the beta 2-adrenoceptor antagonist propranolol, 10 microM, had no effect on the dose-response curve for dimaprit-induced relaxation of the lung strip. The dose-response curve for dimaprit was shifted to the right in a dose-dependent manner by increasing concentrations of a variety of H2-antagonists. Schild plots produced a straight line for all the H2-antagonists with slopes not significantly different from unity. The equilibrium dissociation constants for the H2-antagonists on the lung strip preparation were similar to those previously reported for inhibition of the chronotropic activity of histamine on guinea-pig right atria and inhibition of [3H]-tiotidine binding to homogenates of guinea-pig lung parenchyma.

Animals↗
PubMed1985

The binding of [3H]-tiotidine to homogenates of guinea-pig lung parenchyma.

By use of a rapid filtration assay, the binding of [3H]-tiotidine to homogenates of guinea-pig lung parenchyma was found to be saturable and of a high affinity. Mean values for the KD and Bmax were calculated as 8.5 +/- 1.5 nM and 28 +/- 5 fmol mg-1 protein respectively. The association and dissociation rate constants for [3H]-tiotidine binding at 4 degrees C were calculated to be 0.81 +/- 0.06 microM min-1 and 0.063 +/- 0.005 min-1 respectively, yielding a kinetically derived KD of 7.8 nM. A wide range of H2-receptor agonist and antagonists displaced [3H]-tiotidine binding from lung parenchyma homogenates in a biphasic manner. Examination of the first phase of the displacement of [3H]-tiotidine yielded Ki values for the antagonists tested similar to those found in other binding studies using this ligand and similar to KB values calculated for the antagonists in pharmacological studies.

Animals↗
PubMed1985

The ability of thapsigargin and thapsigargicin to activate cells involved in the inflammatory response.

The ability of thapsigargin and thapsigargicin to activate mast cells and leukocytes has been investigated. The thapsigargin-induced histamine release from rat peritoneal mast cells was found to be dependent on the concentration of thapsigargin, the purity of the mast cell preparations, and the number of mast cells in suspension. Thapsigargin induced histamine release from human basophil leukocytes. Thapsigargin induced beta-glucuronidase and lysozyme release from human neutrophil leukocytes. Thapsigargin caused a release of histamine from mesentery, lung, and heart mast cells of the rat, but only to a minor extent from the corresponding guinea-pig cells. Thapsigargicin induced histamine release from mesentery, lung, and heart mast cells of the rat at concentrations from 0.1 microM but provoked only a release from the corresponding guinea-pig cells in the concentration-range 0.16 to 1.6 microM. Thapsigargin increased the cytoplasmic free calcium level in intact human blood platelets at concentrations from 3.0 nM.

Adult↗
PubMed1985

Contraction of guinea-pig lung parenchymal strips by substance P and related peptides.

A dose-response relationship for substance P and contraction of the lung parenchyma strip of the guinea-pig could only be obtained in the presence of a mixture of bacitracin, 1,4 dithio-L-threitol and ethylenediamine tetracetic acid, all at 100 microM, or in the presence of captopril, 1.8 mM. Substance P (50 nM) caused no contraction by itself but produced a shift to the left of the dose-response curve for histamine with a mean dose-ratio of 1.4 +/- 0.2 (S.E. of mean). The peptides physalaemin, eledoisin and kassinin were all approximately equipotent with substance P on the lung strip, in the presence of peptides inhibitors. [D-Pro4, D-Trp7,9,10]-SP4-11, produced dose-related inhibition of the contraction induced by substance P. Substance P activity in guinea-pig lung declined exponentially with a half-time of 2.3 min: bacitracin, dithiothreitol and EDTA (all 100 microM) increased this to 7.2 min and captopril (1.8 mM) to 5.1 min.

Animals↗
PubMed1984

Characteristics of histamine release from isolated rat mast cells: differences when various ligands are used to induce secretion.

Differences are reported in the response of rat peritoneal mast cells to three releasing agents: ovalbumin, to which the rats were actively sensitized, anti-IgE, an immunoglobulin directed against the rat IgE molecule, and IgE chemically dimerized with suberimidate. Both the rate of histamine release and the rate of desensitization were measured for each of the three ligands. The calculated doubling times for the rates of histamine release due to ovalbumin, anti-IgE and dimer were 19.6 sec, 168 sec and 37.7 sec respectively. The calculated half-lives for the rate of desensitization due to ovalbumin, anti-IgE and dimer were 348 sec, 5900 sec and 3450 sec respectively. The three ligands are all believed to act by crosslinking Fc receptors on the cell surface but the pattern of responses obtained varied with the ligand used. It is proposed that some component of the transduction mechanism linking the stimulus to the cell to the subsequent response can distinguish between the various sizes or conformations of Fc receptor aggregates formed on the cell surface.

Animals↗
PubMed1984

The substance P receptor on rat mast cells and in human skin.

(D-Pro4 D- Trp7 ,9,10)SP4-11 (SPA) has been shown to be a competitive antagonist of the histamine releasing action of substance P in rat peritoneal mast cells. Antagonist activity of SPA is expressed in the concentration range 1 to 10 microM, but at higher concentrations SPA releases histamine. SPA inhibits the flare response induced by substance P in human skin but is without effect on the wheal response. Up to 12.5 pmol SPA produces neither wheal nor flare response by itself. The structurally related peptide, kassinin , does not cause histamine release from rat mast cells at concentrations up to 10 microM whereas the methyl ester of substance P was found to 1.6 times more active than substance P in this respect. The findings are discussed in terms of the classification of substance P receptors and the mechanism of wheal and flare in human skin.

Adult↗
PubMed1984

The effect of substance P and related peptides on the guinea-pig lung strip.

Substance P is present in sensory nerves in the lung and we report here its actions on the lung strip. Substance P was shown to produce rapid, small contractions of trhe lung strip at doses from 10(-9) to 10(-5) M, and there was no apparent dose-response relationship. In the presence of a mixture of three inhibitors of substance P breakdown: bacitracin, 1,4-dithio-L- threitol and ethylenediaminetetra-acetic acid all at 10(-4) M, the responses to substance P were greatly increased and dose-response curves could be established. The concentrations producing half maximal effect in the presence of these inhibitors were 6 X 10(-6) M +/- 4 X 10(-6) M. The inhibitors of substance P breakdown were found to have no effect on the histamine dose-response curve: any small shifts obtained were not significant. Chlorpheniramine 10(-6) M and 10(-5) M shifted the histamine dose-response curve to the right producing dose ratios of 100 and 900 respectively. At these doses chlorpheniramine had no effect on the dose-response curve to substance P. A dose of substance P not itself producing a response (5 X 10(-8) M) caused an increase in the size of the responses to histamine. The histamine dose-response curve was shifted to the left in the presence of substance P producing an average dose ratio of 1.4 +/- 0.2. In the presence of the peptidase inhibitors, dose-response curves have also been produced for physalaemin (10(-7) - 10(-5) M) and eledoisin (10(-7) - 10(-5) M).

Animals↗
PubMed1984

Fractionation of mast cell components for studies of ligand-receptor binding at the plasma membrane.

This communication describes a simple procedure for fractionating mast cells producing plasma membranes and intact granules. Mast cells were purified over a bovine serum albumin density gradient and disrupted under conditions in which no histamine was released. Iodinated immunoglobulin E (IgE) bound to the cells served as a marker for the plasma membrane fraction. Employing a discontinuous sucrose gradient the plasma membrane and granule fractions were separated. The specific activity of the IgE binding to the isolated plasma membrane fractions was 10-fold higher compared with that of the IgE binding to intact cells.

Animals↗
PubMed1983

Structure-activity relationships for some substance P-related peptides that cause wheal and flare reactions in human skin.

Substance P (6.25-25 p-mole) produced dose-dependent flare and wheal responses when injected intradermally into the volar surface of the human forearm. The maximum flare response was obtained within the first 3 min of injection and declined thereafter. The wheal response reached a maximum after 12 min following the injection. Only those peptides having one or more basic residues in the N-terminal region were effective in producing a flare reaction. Eledoisin-related peptide and SP1-9 were 17 and 7 times less active than substance P respectively, whilst [D-pro2, D-phe7, D-trp9]SP1-11 was twice as active. The N-terminal tetrapeptide, SP1-4 and eledoisin were inactive in the dose range tested. Wheal-producing activity was not dependent on the presence of basic residues and the rank order of relative potencies was: physalaemin (2.0): [D-pro2, D-phe7, D-trp9]SP1-11 (1.1): SP1-11 (1.0): SP4-11 (0.4): SP1-9 (0.15): eledoisin-related peptide (0.08): eledoisin (0.06). The N-terminal tetrapeptide failed to produce a wheal response in the dose range tested. Substance P was approximately equi-active with poly-L-arginine in the production of wheal and flare and both of these agents were about 10 times more potent than histamine. Adenosine triphosphate (25-400 n-mole) produced dose-dependent wheal and flare responses and was 10,000 times less potent than substance P. Pre-treatment of the subjects with the H1 histamine antagonist, chlorpheniramine, (20 mg I.V.) reduced the wheal and flare responses to substance P. Local anaesthetic injection into the skin reduced the spread of the flare response but did not affect the development of the wheal response. Pre-treatment of the skin with capsaicin reduced the flare but not the wheal response to intradermal injection of histamine. The results are discussed in relation to the mechanism of the 'axon reflex' vasodilatation in skin. This is thought to involve mast cells in addition to substance P-containing primary afferent neurones.

Adenosine Triphosphate↗
PubMed1982

Histamine release induced by dextran: the nature of the dextran receptor.

Dextrans of molecular weight 10(4) to 2 x 10(6) induced histamine release from rat peritoneal mast cells in the presence of calcium (1 mM) and phosphatidyl serine (10 micrograms/ml). Glucose and low molecular weight dextrans inhibited the histamine release induced by high molecular weight dextrans but the inhibition could not be explained in terms of a simple competitive model. Structure-activity relationships for the inhibition of dextran-induced histamine release by a number of saccharides demonstrated that substitution at the C-3, C-4, and C-6 positions of glucose were most important for activity. Inhibition of histamine release by glucose was specific for the dextran stimulus. Soluble IgE and IgG antibodies failed to interfere with histamine release induced by dextran. Phlorizin specifically inhibited the histamine release induced by dextran. Purification of mast cells on albumin or ficoll gradients produced a selective loss of response to dextran which was not due to the removal of non-mast cells but to some change in the mast cells themselves. The possible nature of the dextran receptor is discussed.

Animals↗