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Biomedical subjects

J L Gordon

Publications and source records attributed to J L Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1979

Stimulation of human platelets by carrageenans.

The rank order of four carrageenans tested as inducers of human platelet aggregation was the same (iota greater than lambda greater than gelcarin greater than kappa) as their relative inflammatory potencies in vivo. All four carrageenans caused some precipitation of plasma proteins, and induced aggregation in platelet-rich plasma or washed platelet suspensions. The second phase of aggregation was citrate-dependent and associated with secretion of 5-hydroxytryptamine and lysosomal enzymes. Platelets could provide a useful model for investigating the actions of carrageenans on cell membranes.

Blood Platelets↗
PubMed1979

Granulocyte adhesion to endothelium in culture.

We previously described a model system for studying the adherence of granulocytes to cultured endothelium, and have now investigated the effects of other blood components on granulocyte adhesion in this system. Red cells enhanced adhesion, whereas blood platelets decreased adhesion, and further experiments suggested that endothelial cells secrete a proadhesive factor, particularly if incubated with plasma. We have also investigated the effects of several drugs, and attempted to localize their sites of action. Flavonoid drugs increased adhesion by an effect at the endothelial cell surface, whereas agents that increase cyclic AMP levels, including several prostaglandins, stimulated adhesion mainly by their effects on granulocytes. The effects of some agents on granulocyte adhesion to endothelium were not paralleled by their effects on adhesion to serum-coated glass. We conclude that granulocyte-endothelial interaction is a complex process, with each cell type responding to the other or to factors produced by it, and that data derived solely from studies of granulocyte adhesion to inert substrata will not always reflect granulocyte-endothelial interaction in vivo.

Animals↗
PubMed1979

Granulocyte migration through endothelium in culture.

Using a model system with which we have previously investigated the adhesion of granulocytes to cultured endothelium, we have now shown that adherent granulocytes migrate through cultured endothelium in a manner closely resembling that found during the acute inflammatory response in vivo. The migration of granulocytes was markedly enhanced in the presence of erythrocytes, whereas blood platelets did not affect migration. Several test agents, including Paroven and some prostaglandins, had different effects upon migration and adhesion. We conclude that the adhesion of granulocytes to endothelium and their migration through it are responses that are, at least in part, separately controlled, and that migration does not depend exclusively upon extravascular stimuli.

Animals↗
PubMed1978

Malonaldehyde formation in intact platelets is catalysed by thromboxane synthase.

Imidazole and compound L8027 (selective inhibitors of thromboxane synthase) produced parallel inhibition of malonaldehyde and thromboxane B2 secretion induced by collagen or thrombin in gel-filtered suspensions of human platelets. Comparing the effects of these inhibitors and aspirin on secretion of granule constituents indicated that platelet degranulation depends mainly on thromboxane production; prostaglandin endoperoxides contributed little.

Blood Platelets↗
PubMed1978

Prostaglandin receptors on human platelets. Structure-activity relationships of stimulatory prostaglandins.

1. Synthetic analogues of prostaglandins E2 or F2a (monocyclic bisenoic prostaglandins), like the endogenous prostaglandin endoperoxides (prostaglandins G2 and H2) from platelets, and like synthetic analogues of prostaglandin H2 (bicyclic bisenoic prostaglandins), can induce aggregation of human platelets, although prostaglandins E2 and F2a themselves are inactive. 2. All the prostanoid compounds that induce platelet aggregation release 5-hydroxytryptamine from platelet dense bodies, but do not release beta-N-acetylglucosaminidase from lysosomal granules. Arachidonic acid evokes a similar response. 3. All endoperoxide analogues tested (bicyclic compounds) were powerful platelet stimulants, and all active compounds (whether mono- or bi-cyclid) apparently acted via the same receptor as the endogenous prostaglandin endoperoxides. 4. The nature and stereospecificity of substituents at positions 11 and 15 (or 16) on prostaglandin E2 are critical determinants for platelet-stimulating activity: deoxy substitution at position 11 plus methylation at position 15 (or 16) produces a potent stimulant, particularly if the groups around C-15 are in the S configuration. 5. The effects of these structural modifications are apparently due to, at least in part, a change in side-chain conformation.

Adenosine Diphosphate↗
PubMed1978

Uptake and metabolism of adenosine by pig aortic endothelial and smooth-muscle cells in culture.

1. Adenosine, a potent vasodilator, is transported very efficiently by pig aortic endothelium in monolayer culture (approx. 50pmol/min per 10(6) cells at 2 micrometer). Uptake proceeds by diffusion at high (millimolar) substrate concentrations, and by two discrete transport processes (Km approx. 3 micrometer and 250 micrometer) at lower concentrations. Over 90% of the adenosine taken up at 10 micrometer or 100 micrometer is rapidly converted into adenine nucleotides (mainly ATP). 2. The high-affinity process is selectively inhibited by dipyridamole and by nitrobenzylthioinosine. Adenine preferentially inhibits the lower-affinity process, papapaverine inhibits both transport processes, and inosine has no significant effect. 3. Pig aortic smooth-muscle cells in culture show no high-affinity transport system for adenosine; uptake is much slower at low concentrations than that by endothelium (approx. 5pmol/min per 10(6) cells at 2 micrometer). Over 80% of the incorporated adenosine at 10 micrometer or 100 micrometer is rapidly converted into adenine nucleotides. 4. The uptake of adenosine by smooth-muscle cells is powerfully inhibited by adenine, but dipyridamole is much less potent than in endothelium. 5. We conclude that endothelial cells are mainly responsible for the removal of circulating adenosine.

Adenine↗
PubMed1978

5-Hydroxytryptamine and dopamine transport by rat and human blood platelets.

1 Uptake of 5-hydroxytryptamine (5-HT) by rat platelets in plasma was very rapid and diffusion did not contribute significantly at substrate concentrations that did not saturate the active transport.2 Under conditions which allowed measurement of initial rates of uptake, kinetic analysis revealed a high affinity uptake mechanism for 5-HT (K(m) = 0.7 muM).3 Uptake of dopamine was relatively slow and involved a lower affinity (K(m) = 70 muM) active transport process. Diffusion contributed significantly at concentrations that did not saturate the active transport.4 5-HT competitively inhibited uptake of dopamine, and vice versa; K(i) values for both amines were similar to their respective K(m) values for uptake.5 Chlorimipramine, desmethylimipramine and benztropine were tested as uptake inhibitors. Each was equipotent against 5-HT and dopamine, although the absolute potency of the drugs varied greatly. Chlorimipramine was the most potent (K(i)## 100 nM), and kinetic analysis revealed that the inhibition was competitive against both 5-HT and dopamine.6 Similar results were obtained in studies with human platelets: K(m) values for 5-HT and dopamine were about 1 muM and 100 muM respectively. Activity profiles of inhibitors were also similar: each compound tested was equipotent against 5-HT and dopamine, and the two amines each competitively inhibited uptake of the other.7 We conclude that dopamine is actively transported by platelets via the 5-HT uptake mechanism, but with a much lower affinity. There is no high-affinity dopamine-specific mechanism corresponding to that in the corpus striatum. Consequently although platelets may be valid models of transport in 5-hydroxytryptaminergic neurones, they should not be regarded as models for the dopamine transport mechanism found in dopaminergic neurones.

Animals↗
PubMed1978

Effects of sulphinpyrazone and aspirin on prostaglandin I2 (prostacyclin) synthesis by endothelial cells.

Synthesis of prostaglandin I2, (PGI2, prostacyclin) by vascular endothelium (assayed by the ability of cultured endothelial cells to inhibit platelet aggregation) was inhibited by aspirin. At 100 mumol/l aspirin completely blocked measurable PGI2 production, but endothelial cells had substantially recovered their ability to synthesize PGI2 24 h after removal of the drug. In contrast, the effect of 1 mmol/l aspirin was still evident 24 h after drug withdrawal. Sulphinpyrazone also inhibited PGI2 synthesis, but was about 100 fold less potent than aspirin, and the effect of the drug was lost within 24 h of its addition, even when endothelial cells were left in contact with the drug during this period.

Aspirin↗