PubMed Health⌕ Search

Biomedical subjects

G V Born

Publications and source records attributed to G V Born.

12 recordsLinked to original sources
PubMed1979

Effects of D- and L- enantiomers of adenosine, AMP and ADP and their 2-chloro- and 2-azido- analogues on human platelets.

Aggregation of human platelets by ADP and the inhibition of this effect by adenosine are apparently mediated by different receptors. One of the criteria for receptors is that they show stereospecificity for their ligands. We have synthesized L-enantiomers of D-adenosine, AMP and ADP, together with their corresponding photolysable 2-azido analogues so that platelet receptors could be tested for stereospecificity. All of the L-enantiomers were completely inactive as aggregators or inhibitors of platelet function. None of the L-enantiomers changed levels of platelet cAMP. 2-Azido-L-adenosine, AMP and ADP are proposed as useful controls in photoaffinity experiments for non-specific labelling.

Adenosine↗
PubMed1979

Inhibition of platelet thrombus formation by chlorpromazine acting to diminish haemolysis.

There is increasing evidence that the sudden, unpredicatable event initiating myocardial infarction is fissuring of an atherosclerotic plaque. The resulting haemorrhage into the arterial wall produces obstructive platelet thrombi, just as arterial haemorrhages elsewhere produce haemostatic platelet plugs. It has been suggested that such platelet aggregation depends on ADP originating in red cells which are subjected to excessive haemodynamic stress at the site of haemorrhage. The release of ADP from red cells has been demonstrated in vitro in equivalent condtions of shear stress; and other mechansims, such as activation by collagen, cannot account for the rapidity with which the platelets react. One of us (G.V.R.B.) has suggested that drugs capable of counteracting haemolysis might diminish the activating effect of erythrocytes on platelets and so inhibit their aggregation as thrombi. Thus, chlorpromazine, added to human blood at concentrations which diminish haemoylsis but do not directly affect platelet aggregation, prolonged the 'bleeding time' from small holes in artificial vessels where extravasation is terminated, as in living arterioles, by aggregated platelets. The bleeding time was also prolonged by apyrase, consistent with the conclusion that the chlorpromazine acted through decreasing plasma ADP. We show here that this occurs through the anti-haemolytic action of chlorpromazine.

Adenosine Diphosphate↗
PubMed1978

Quantification of the morphological reaction of platelets to aggregating agents and of its reversal by aggregation inhibitors.

1. In rabbit citrated platelet-rich plasma, the changes in shape of the platelets produced by adenosine diphosphate (ADP) or 5-hydroxytryptamine (5-HT) were observed by photometric and volumetric techniques and by measurements of platelet images on electron micrographs either directly or with an image analysing computer. This permitted the indirect manifestations of the shape changes to be correlated with the morphological features responsible for them, i.e. transformation of disks to more spherical forms and extrusion of blebs and spikes. 2. Following the addition of ADP, an initial brief peak in the light scattering records was associated with marked but transient irregularities in the surface of the platelets. These effects were absent when the other shape changes were produced by 5-HT. 3. When the optical manifestations of the shape changes induced by ADP were reversed by the addition of antagonists adenosine triphosphate, 2-chloroadenosine or prostaglandin E1, the morphological changes were reversed by a diminution in the number of spikes and the conversion of spherical platelet bodies to a more discoid form. 4. The volume of extracellular plasma trapped between platelets sedimented by centrifugation was proportional to the number of spikes which they extruded. Under all conditions, the volume of the platelets themselves remained remarkably constant at approximately 5 X 10(-9) microliter./platelet. 5. Addition of a calcium chelating agent alone produced a rapid persistent alteration in the optical properties of platelet-rich plasma. The magnitude of this alteration was proportional to chelator concentration but greater in some plasmas than in others. Similar optical effects were produced when the calcium concentration of platelet-rich plasma was increased by adding calcium. The optical effects produced by calcium or its chelators were unusual in that the changes in transmitted and horizontally scattered light were in opposite directions (transmitted light decreased, scattered light increased) whereas, in all other circumstances so far examined, these changes were in the same direction. The chelators caused the formation of spikes on the platelets without appreciably altering their disk shape, which may explain the unusual nature of the optical effects.

Adenosine↗
PubMed1976

Relation between the inhibition of aggregation and the concentration of cAMP in human and rat platelets.

Adenosine inhibits the aggregation of human but not of rat platelets whereas both are inhibited by prostaglandin E1 or by the pyrimido-pyrimidine compound RA233. In human platelets all three agents increase adenosine-3'-5'-cyclic monophosphate (cAMP). If the inhibition of aggregation depended on this increase, adenosine might be expected not to increase cAMP in rat platelets. Under conditions in which adenosine inhibited aggregation and increased cAMP in human platelets, adenosine caused a similar increase in cAMP in rat platelets without inhibiting their aggregation. The aggregation of rat platelets was inhibited as effectively as that of human platelets by PGE1 or RA233 at concentrations which caused greater increases in cAMP than did the highest concentrations (2.8 X 10(-4) M) of adenosine it was possible to use. When the increase of cAMP in rat platelets by PGE1 was limited to that produced by adenosine, PGE1 like adenosine failed to inhibit aggregation. Therefore, the difference in the inhibitory effectiveness of adenosine on rat and human platelets was quantitative rather than qualitative and apparently depended on the inability of adenosine to increase cAMP sufficiently in rat platelets. When cAMP had been increased by adenosine, PGE1 or RA233, the addition of ADP caused cAMP to decrease rapidly in both human and rat platelets to between +22 and -18% of control values, except that the decrease in rat platelets was to +40% after RA233 had been present for 0.5 min before ADP. The increase in cAMP produced in rat platelets by adenosine at 5 X 10(-6) to 2.8 X 10(-4) M for 3 min was associated with a small increase in aggregation velocity. It is suggested that the comparative ineffectiveness of adenosine as an inhibitor of platelet aggregation, particularly with rat but less so also with human platelets, is because, unlike PGE1 or RA233, adenosine has two opposing actions on aggregation; one being inhibition by activating adenylate cyclase and increasing cAMP, and the other being potentiation by uptake. This hypothesis accounts for the present results as well as for the earlier observation that dipyridamole which prevents the uptake of adenosine potentiates its inhibitory effect on the aggregation of human platelets.

Adenosine↗