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J C Foreman

Publications and source records attributed to J C Foreman.

At least 55 records · Page 3Linked to original sources
PubMed1989

The stimulation of IL-2 production by anti-rheumatic drugs.

IL-2 release from mouse splenocytes was measured by assaying the IL-2 on an IL-2-dependent cytotoxic T-lymphocyte line in culture (CTLL). Proliferation of the CTLL cells was monitored indirectly with the dye thiazolyl blue. The slow-acting anti-rheumatic drug auranofin at concentrations below 0.1 microM potentiated concanavalin A (Con A)-induced IL-2 release. Similar potentiation of Con A-induced IL-2 release was obtained with D-penicillamine, 1 microM-1 mM, and with the angiotensin-converting enzyme-inhibitor captopril, 10 nM-1 microM. Potentiation of Con A-induced IL-2 release was obtained with concentrations of the drugs likely to be achieved in vivo during therapy. Auranofin but not D-penicillamine and captopril inhibited Con A-induced IL-2 release at high concentrations (greater than 0.3 microM).

Animals↗
PubMed1988

A simple quantitative fluorimetric assay of in vitro phagocytosis in human neutrophils.

In general the in vitro assays of phagocytosis rely on microscope counting or radioisotopic detection of ingested particles or microbiological counting of non-ingested bacteria. A very simple, rapid, highly quantitative method using fluorescein-labelled bacteria was described by Vray et al. (Scand. J. Immunol. (1980) 11, 147) for non-human phagocytes. We report here a modification of this method to increase its sensitivity, to make it more suitable for pharmacological studies. We also provide detailed experimental parameters for its use with human phagocytes. A suspension of fluorescein-labelled bacteria is incubated with human phagocytes; after incubation at 37 degrees C, the reaction is terminated with ice-cold Tyrode buffer solution, and the non-ingested bacteria are removed by lysis with lysozyme and the resultant cell suspension treated with the detergent TX-100. The fluorescence of the suspension is then measured. The modified method is sufficiently sensitive to permit the detection of bi-directional effects on phagocytosis of a known modulator of human phagocyte function.

Auranofin↗
PubMed1988

Desensitization of rat peritoneal mast cells to substance P.

Rat peritoneal mast cells were pretreated for 10 min at 37 degrees C with either substance P (SP, 3 or 6 microM) or compound 48/80 (37.5, 50 or 75 ng/ml). The effect of this pretreatment on the subsequent responsiveness of the cells to SP was studied. Both SP and compound 48/80 pretreatment of rat peritoneal mast cells inhibited the subsequent response of the cells to SP. The degree of inhibition produced by either SP or compound 48/80 was dependent on the concentration used to pretreat the cells. Inhibition of the response of the cells to SP was observed whether or not the pretreating agent was removed or remained in contact with the cells during the subsequent stimulation with SP. It is concluded that compound 48/80 and SP desensitize the cells to subsequent stimulation by SP and possible mechanisms for this are discussed.

Animals↗
PubMed1988

The skin as an organ for the study of the pharmacology of neuropeptides.

There is good evidence that some vascular effects of inflammation in the skin are neurogenic and involve axon reflexes in the terminal arborizations of C-fibres containing substance P, neurokinin A and calcitonin gene-related peptide (CGRP). Substance P produces dose-related wheal and flare reactions in human skin. Neurokinin A induces wheal but little or no flare and is less potent than substance P. CGRP induces both wheal and flare but is also less potent than substance P. In addition, CGRP induces a slow-onset, intense vasodilatation in human skin which persists for several hours and is associated with leucocyte infiltration: a response which is not seen with substance P. Substance P also releases histamine from mast cells in the skin and the presence or absence of a role for histamine and mast cells in neurogenic inflammation in skin is discussed.

Animals↗
PubMed1987

Phorbol esters induce a slow, non-cytotoxic release of histamine from rat peritoneal mast cells.

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the synthetic diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG) were employed to investigate the consequences of protein kinase C activation in rat peritoneal mast cells. TPA (10 ng/ml) induced a biphasic release of histamine from mast cells. At short periods of incubation histamine release was low; about 10% at 10 min. At 15 min a second phase of release commenced, achieving a maximum at 90 min incubation by which time about 70% of cell histamine was released. Histamine release by TPA was dependent on glycolytic and oxidative metabolism, temperature-dependent and occurred in purified mast cells. In contrast, histamine release induced by OAG 50 micrograms/ml was maximal after 20 min. Studies using RHC 80267, a diacylglycerol (DAG) lipase inhibitor, indicated that metabolism of OAG by DAG lipase as well as spontaneous degradation accounts for the comparatively short-lived response to OAG.

Animals↗
PubMed1987

Action of the SP2-11 and SP3-11 fragments of substance P on rat peritoneal mast cells.

The ability of the SP fragments SP2-11 and SP3-11 to release histamine from rat peritoneal mast cells has been compared with that of the whole peptide. SP1-11 was found to be about 3.4 times more active than SP2-11 and about 10.4 times more active than SP3-11. The substance P antagonist [D-Pro4, D-Trp7,9,10] SP4-11 was equally effective at antagonizing the histamine releasing action of SP1-11, SP2-11 and SP3-11. Benzalkonium chloride was found to be a competitive antagonist of SP and SP3-11: the dissociation constants for the benzalkonium chloride-receptor interaction being about the same when either SP1-11 or SP3-11 was used as the agonist.

Animals↗
PubMed1987

The actions of inhibitors of diacylglycerol kinase and diacylglycerol lipase on histamine release from rat peritoneal mast cells.

1. RHC 80267 and R59 022 are selective inhibitors of diacylglycerol (DAG) lipase and DAG kinase enzymes respectively. These inhibitors were examined with regard to their effects on oleoylacetylglycerol (OAG)-and anti-IgE- induced histamine secretion in rat peritoneal mast cells. 2. RHC 80267, 10 microM and R59 022, 50 microM both enhanced OAG-induced histamine release by 30% and 40% respectively. 3. In the concentration range 3-30 microM, R59 022 enhanced anti-IgE-induced histamine release by up to about 40%, whereas RHC 80267 was without effect. 4. The enhancement of anti-IgE-induced histamine release by R59 022 is consistent with a role for protein kinase C in transducing immunological signals to rat peritoneal mast cells. 5. The lack of effect of RHC 80267 in this situation may indicate that in the mast cell, DAG kinase is more active than DAG lipase in degrading physiological levels of DAG.

Animals↗
PubMed1987

The activity of compounds extracted from feverfew on histamine release from rat mast cells.

An extract of the plant feverfew (Tanacetum parthenium) produces a dose-dependent inhibition of histamine release from rat peritoneal mast cells stimulated with anti-IgE or the calcium ionophore A23187. Greater inhibition of anti-IgE-induced histamine release was achieved with feverfew compared with the inhibition of A23187-induced release. Inhibition of anti-IgE-induced histamine release by feverfew extract was observed when the drug was added simultaneously with anti-IgE and the inhibitory activity increased only slightly when the drug was preincubated with the cells for 5 min before anti-IgE stimulation. In this respect feverfew differs from cromoglycate and quercetin. Feverfew extract inhibited anti-IgE-induced histamine release to the same extent in the absence and presence of extracellular glucose. It is concluded that feverfew extract contains a novel type of mast cell inhibitor.

Animals↗
PubMed1987

Substance P and calcitonin gene-related peptide: effects on mast cells and in human skin.

Mast cells are found in close association with blood vessels, and histamine is known to be a potent vasodilator in humans. It is now clear that mast cells form neuroeffector junctions and that one of the types of nerve involved is the peptide-containing primary afferent neurone (C fibre). Nerve stimulation produces vasodilation which is blocked by antihistamines or by depletion of mast cell histamine with compound 48/80. Nerve stimulation also releases histamine and degranulates mast cells. Substance P and other neuropeptides release histamine from isolated rat and human skin mast cells. The actions of substance P and calcitonin gene-related peptide in human skin are compatible with a role for these two peptides in neurogenic inflammation. The inflammatory effects of substance P in human skin are inhibited by antihistamines. The possible role of the mast cell in neurogenic inflammation is discussed.

Animals↗
PubMed1987

Protein and diacylglycerol phosphorylation in the stimulus-secretion coupling of rat mast cells.

The pattern of endogenous protein phosphorylation during stimulation of rat peritoneal mast cells by two types of agonists has been compared. Compound 48/80, substance P and histone, which do not require the presence of external Ca2+ to trigger histamine release, induced a similar profile of phosphorylation comprising an increased phosphorylation of a 35,000 molecular weight (MW) protein and dephosphorylation of a 15,000 MW protein. The same profile was seen when the cells were stimulated with phorbol-12-myristate-13-acetate. The phorbol ester also induced histamine release, although less than that caused by the other secretagogues. The pattern of phosphorylation shared by both the phorbol ester and the basic secretagogues represented only part of that observed when the cells were stimulated in a Ca2+-free medium with anti-IgE. Under those conditions, two additional proteins of 68,000 and 56,000 MW became phosphorylated. The phosphorylation of these two proteins increased when anti-IgE was applied in the presence of Ca2+. In contrast, the extent of phosphorylation of the 35,000 MW protein was diminished. Both the basic secretagogues and anti-IgE, but not the phorbol ester, also enhanced the production of phosphatidic acid, indicating that diacylglycerol was generated. This process was independent of the presence of external Ca2+. It is suggested that protein kinase C activation is responsible for the phosphorylation observed with the basic secretagogues but not entirely with IgE-directed ligands.

Animals↗
PubMed1987

Histamine release induced by Arg-Pro-Lys-Pro(CH2)11CH3 from rat peritoneal mast cells.

The substance Arg-Pro-Lys-Pro-(CH2)11CH3 [SP1-4C12] was synthesized by forming a peptide bond between Arg-Pro-Lys-Pro, the N-terminal sequence of substance P and dodecylamine. The aim was to examine the roles of the N- and C-terminal sequences of substance P in stimulating histamine release from mast cells of the rat peritoneal cavity. SP1-4 C12 induces concentration-dependent histamine release in the range 8 to 200 nM. SP1-4C12 was 50 times more potent than substance P and 300 times more potent than dodecylamine. Unlike dodecylamine itself, SP1-4C12 induced noncytolytic histamine release which was inhibited by benzalkonium chloride and by the substance P antagonist [D-Pro4,D-Trp7,9,10]SP4-11. Histamine release induced by SP1-4C12 was inhibited at temperatures below 16 degrees C and did not require the presence of extracellular calcium ions. It is suggested that substance P and some other basic histamine liberators initiate histamine secretion by a mechanism that involves the insertion of a hydrophobic region into the membrane lipid which is necessary to present positively charged moieties to a receptor site involved in activating the secretory mechanism.

Animals↗
PubMed1986

Some studies of the action of betahistine at H1 and H2 receptors for histamine.

Betahistine produced a concentration-dependent contraction of the guinea-pig ileum and was about 27 times less active than histamine in this respect. Betahistine induced desensitization of contractile responses to histamine in the guinea-pig ileum. The H1 histamine receptor antagonist mepyramine was a competitive antagonist of the action of betahistine on the guinea-pig ileum. Betahistine caused relaxation of the rat uterus contracted by acetylcholine, and this action of betahistine was blocked by the H2 receptor antagonist cimetidine. Betahistine had a concentration-dependent positive chronotropic action on isolated guinea-pig atria, and in this respect was tenfold less potent than histamine. The action of betahistine on the atria was blocked by the H2 receptor antagonist YM11170. Betahistine caused a concentration-related contraction of the isolated lung parenchymal strip of the guinea-pig, and YM11170 potentiated this effect. Betahistine failed to release histamine from rat peritoneal mast cells at concentrations up to 100 microM and it did not prevent histamine release induced by either substance P or anti-IgE. Betahistine produced a dose-related flare and wheal reaction when injected intradermally into human skin. It is concluded that betahistine has agonist activity at both H1 and H2 receptors for histamine.

Animals↗
PubMed1986

Characteristics of the effect of phorbol ester on rat mast cells: interaction with anti-IgE.

The phorbol ester 12-0-tetradecanoyl-13-acetate (TPA) induced a dose-dependent release of histamine from rat peritoneal mast cells at concentrations from 3 to 100 ng/ml. The release is biphasic: an early phase being complete in 15 min and being followed by a second phase extending for more than 50 min. Concentrations of TPA greater than 100 ng/ml produced decreasing releases of histamine. Synergistic interaction in the induction of histamine secretion was observed between TPA and A23187 and between TPA and anti-IgE. Such synergism with anti-IgE was only manifest at low concentrations of TPA and with incubations of the cells with TPA for 5 mins or less. At higher concentrations of TPA and longer incubations, TPA inhibited the response of rat peritoneal mast cells to anti-IgE stimulation. Synergism between A23187 and TPA was observed only at low levels of histamine release induced by calcium plus A23187: at higher levels of release TPA was inhibitory.

Animals↗
PubMed1986

Some effects of calcitonin gene-related peptide in human skin and on histamine release.

Calcitonin gene-related peptide (CGRP) produced a dose-related wheal and flare reaction in human skin at doses of 12.5 to 50 pmol. The flare response but not the wheal response to CGRP and substance P were inhibited by prior treatment of the subject with oral chlorpheniramine, 16 mg. CGRP, but not substance P, was potent in producing a delayed erythema and surrounding pallor in human skin, which peaked at 1 h and persisted for more than 3 h after injection, when wheal and flare responses had subsided. The delayed response was accompanied by infiltration of polymorphonuclear leukocytes. The delayed erythema and pallor produced in response to CGRP were not inhibited by oral chlorpheniramine, or by 4% prilocaine injected locally. CGRP released histamine from rat peritoneal mast cells over the concentration range 2.5-10 microM. CGRP was about fourfold less potent than substance P in releasing histamine. The substance P analogue, [D-Pro4, D-Trp7,9,10]SP4-11 10 microM, and benzalkonium chloride 10 microM inhibited histamine release from rat mast cells stimulated by either CGRP or substance P.

Adult↗
PubMed1986

A study of the H2-receptor for histamine stimulating adenylate cyclase in homogenates of guinea-pig lung parenchyma.

The effect of forskolin and several H2-agonists was investigated on the activity of adenylate cyclase in homogenates of guinea-pig lung parenchyma. Histamine, 0.1 microM to 1 mM, dimaprit, 1 microM to 10 mM, 4-methyl histamine, 0.1 microM to 10 mM, impromidine, 10 nM to 10 microM and forskolin, 1 nM to 100 microM, all produced a dose-dependent stimulation of adenylate cyclase activity above the basal level. The histamine H1-receptor antagonist mepyramine, 10 microM, and beta-adrenoceptor antagonist propranolol, 10 microM, had no effect on the stimulation by histamine of adenylate cyclase. The dose-response curve for stimulation by histamine of adenylate cyclase was shifted to the right in a dose-dependent manner by increasing concentrations of several H2-antagonists. Schild plots constructed for each H2-antagonist produced straight lines with slopes not significantly different from unity. The equilibrium dissociation constants obtained for the H2-antagonists in this study were similar to those previously reported for inhibition of dimaprit-induced relaxation of the pre-contracted lung strip, inhibition of [3H]-tiotidine binding to homogenates of guinea-pig lung parenchyma and inhibition of histamine-stimulated adenylate cyclase in guinea-pig gastric mucosa.

Adenylyl Cyclases↗
PubMed1986

Comparison of the histamine-releasing action of substance P on mast cells and basophils from different species and tissues.

The action of the neuropeptide substance P as a histamine-releasing agent has been compared in histamine-containing cells from a variety of different tissues and species. Peritoneal mast cells from rat, mouse and hamster but not human cells gave a concentration-dependent release of histamine in response to substance P. Release was greater in the absence than in the presence of calcium in the extracellular medium. Mast cells from rat mesentery, lung and heart released histamine in response to substance P, but heart mast cells responded only weakly. All guinea-pig mast cells and histamine-containing cells from human tissues did not give any substantial substance-P-induced release of histamine. The data provides further evidence for the functional heterogeneity of histamine-containing cells.

Animals↗