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Biomedical subjects

R J Flower

Publications and source records attributed to R J Flower.

At least 199 records · Page 11Linked to original sources
PubMed1979

Effects of modulators of arachidonic acid metabolism on the synthesis and release of slow-reacting substance of anaphylaxis.

1 Slow-reacting substance of anaphylaxis (SRS-A) was released in the peritoneum of passively sensitized rats challenged with ovalbumin and from rat isolated peritoneal cells stimulated with calcium ionophore A23187. 2 Both monocytes (macrophages) and mast cells appear to be involved in the synthesis and release of SRS-A. 3 The immunological release of SRS-A in vivo is enhanced by indomethacin and inhibited by dexamethasone, mepacrine, 1-phenyl-3-pyrazolidone (1-P-3-P), and methylimidazole. 4 SRS-A release induced by A23187 in vitro is inhibited by dexamethasone, indomethacin 1-P-3-P, eicosatetraynoic acid (ETA) and 15-hydroperoxy arachidonic acid. The inhibition induced by dexamethasone, indomethacin and 1-P-3-P is reduced by an increase in the calcium concentration from 1 mM to 5 mM, whereas the inhibition induced by ETA is increased. 5 The results suggest that a lipoxygenase is important in the synthesis and release by SRS-A.

Animals↗
PubMed1978

The effect of bradykinin on the electrical activity of rat jejunum.

Bradykinin increased the potential difference across both the jejunum and colon of the rat. This effect was significantly reduced by indomethacin, suggesting that it was mediated by prostaglandins. The possibility that bradykinin may contribute to the diarrhoea of the carcinoid syndrome by inducing a net secretory state in the intestine is discussed.

Animals↗
PubMed1978

Further studies on the enzymatic conversion of prostaglandin endoperoxide into prostacyclin by porcine aorta microsomes.

A simple, rapid radiochemical assay for prostacyclin synthesis has been used to characterize the enzyme in arterial walls which converts prostaglandin endoperoxides to prostacyclin. The enzyme displays a broad pH optimum, and catalyses a rapid conversion of saturating concentrations of the endoperoxide at 37 degrees C. Hydroperoxides of several unsaturated fatty acids are potent inhibitors of the enzyme, and act in a time dependent manner. The isomerase which converts prostaglandin endoperoxides to prostaglandin E2 or D2 was not detected in the arterial wall.

Animals↗
PubMed1978

Phospholipase A2 activity of guinea-pig isolated perfused lungs: stimulation, and inhibition by anti-inflammatory steroids.

1 A simple double-isotope assay for phospholipase A2 activity of perfused organs is described; Guinea-pig lungs perfused through the pulmonary circulation exhibit a low background enzyme activity. This activity is blocked by dexamethasone, betamethasone and hydrocortisone, mepacrine, procaine or chlorpromazine. Aspirin and indomethacin are without effect. 3 Mechanical trauma, antigen challenge or injections of bradykinin, rabbit aorta contracting substance-releasing factor (RCS-RF) or histamine increase "basal" phospholipase activity. The effect of these agents, except that of bradykinin, is blocked by dexamethasone or mepacrine. 4 The blocking effect of steroids is cumulative and dose-dependent. They do not work in cell-free systems. Inhibition by mepacrine is rapid and is effective in cell-free lung homogenates. 5 It is suggested that agents which liberate prostaglandin endoperoxides and thromboxane A2 from perfused lungs do so by activating phospholipase A2.

Animals↗
PubMed1977

The role of prostaglandins in parturition, with special reference to the rat.

The evidence which suggests a role for prostaglandins in parturition is reviewed, with special reference to experimental observations on the rat. The pregnant uterus can both synthesize and metabolize prostaglandins. The biosynthetic capacity of the rat uterus increases as pregnancy proceeds. This increase, which is especially marked during the last few days of pregnancy, may be oestrogen-controlled. During pregnancy the tissue levels of the major prostaglandin-metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (EC 1.1.1.141) is greatly increased. This may prevent aberrant production of prostaglandins from terminating the pregnancy prematurely. The capacity for prostaglandin metabolism begins to fall (perhaps under hormonal control) as the expected day of delivery approaches; this, coupled with an augmented biosynthesis, produces a net increase in uterine prostaglandins which contribute to the process of parturition by causing a decrease in progesterone concentration, increasing the muscular tone of the uterus, and altering uterine haemodynamics. Agents which block either prostaglandin synthesis or metabolism delay or accelerate the parturition process in the rat.

Animals↗
PubMed1977

Synthesis of 6-keto-PGF1alpha by ram seminal vesicle microsomes.

At low substrate/enzyme ratios, and in the absence of reduced glutathione (GSH), the major prostaglandin (PG) biosynthesised by the ram seminal vesicle cyclo-oxygenase from arachidonic acid was 6-keto-PGF1alpha. The addition of nanomolar amounts of reduced GSH suppressed biosynthesis of this product and stimulated the formation of PGE2; 1-epinephrine enhanced the conversion of the substrate but had no effect on the type of product formed. 15-Hydroperoxy arachidonic acid selectively inhibited formation of 6-keto-PGF1alpha (IC50 100 muM) but blocked synthesis of all cyclo-oxygenase products at concentrations greater than 1 mM. At substrate concentrations of muM or greater, synthesis of 6-keto-PGF1alpha was inhibited and PGE2 and PGF2alpha were the main products formed.

Animals↗
PubMed1977

The distribution and metabolism of arachidonic acid in rabbit platelets during aggregation and its modification by drugs.

1 Gas chromatographic and radio-isotope labelling techniques have been used to establish the origin of the arachindonic acid used by the platelet cyclo-oxygenase for the synthesis of pro-aggregatory prostaglandin endoperoxide derivatives. 2 Measurements of total platelet arachidonate content indicated that more than 95% is esterified in the phosphatide fraction of the cells. 3 During aggregation by collagen or thrombin as much as 80% of the total platelet arachidonate may be liberated and transformed by the platelet enzymes into hydroxyacids and other more polar compounds. 4 The phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol fractions are major sources of the arachidonate thus used. 5 Indomethacin, which prevents platelet aggregation by inhibiting the cyclo-oxygenase, did not affect this release of arachidonate from the phosphatides but did prevent the transformation of arachidonate to endoperoxide derivatives. 6 Mepacrine, a drug which possesses weak anti-phospholipase activity in platelets, also prevents aggregation by collagen or thrombin, but seems to do so by preventing substrate release from the phosphatide fraction. 7 It is suggested that phospholipase A2 plays a key role in the initial events during platelet aggregation induced by collagen.

Animals↗