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British Journal of Haematology May 1976Adenosine 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... (Comparative Study)
Comparative Study
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.
Topics: Adenosine; Adenosine Diphosphate; Animals; Blood Platelets; Cyclic AMP; Humans; In Vitro Techniques; Mopidamol; Platelet Aggregation; Prostaglandins E; Rats
PubMed: 178342
DOI: 10.1111/j.1365-2141.1976.tb00969.x -
Nihon Ketsueki Gakkai Zasshi : Journal... Feb 1976
Topics: Bencyclane; Blood Platelets; Cyclic AMP; Cycloheptanes; Humans; In Vitro Techniques; Mopidamol; Platelet Aggregation; Pyrimidines; Serotonin; Vasodilator Agents
PubMed: 183446
DOI: No ID Found -
Die Medizinische Welt Jan 1976
Comparative Study
Topics: Animals; Blood Coagulation; Carcinoma 256, Walker; Dipyridamole; Dose-Response Relationship, Drug; Ketones; Mopidamol; Neoplastic Cells, Circulating; Rats; Surface Properties; Xanthines
PubMed: 1250120
DOI: No ID Found -
The Annals of Thoracic Surgery Jan 1976Dogs subjected to a thoracotomy in which a rib-spreading retractor was employed developed filling defects in the cerebral microcirculation attributable to obstruction by...
Dogs subjected to a thoracotomy in which a rib-spreading retractor was employed developed filling defects in the cerebral microcirculation attributable to obstruction by microemboli. These changes were not observed in control groups and could be prevented in the experimental group by pretreatment with RA233, a platelet inhibitor. It is possible that microembolic-related complications of operations and trauma, such as pulmonary insufficiency, might be ameliorated by the use of platelet inhibitors.
Topics: Animals; Brain; Dogs; Intracranial Embolism and Thrombosis; Microcirculation; Mopidamol; Postoperative Complications; Pyrimidines; Thoracic Surgery; Thorax
PubMed: 1247322
DOI: 10.1016/s0003-4975(10)64885-0 -
Life Sciences Nov 1975
Relative potencies of dipyridamole and related agents as inhibitors of cyclic nucleotide phosphodiesterases: possible explanation of mechansim of inhibition of platelet function.
Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenosine; Blood Platelets; Cyclic GMP; Dipyridamole; Humans; Mopidamol; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Platelet Adhesiveness; Platelet Aggregation; Pyrimidines
PubMed: 173959
DOI: 10.1016/0024-3205(75)90170-8 -
[Rinsho Ketsueki] the Japanese Journal... Apr 1975
Topics: Anti-Inflammatory Agents; Bencyclane; Blood Platelets; Halofenate; Humans; Imipramine; In Vitro Techniques; Mopidamol; Platelet Adhesiveness; Platelet Aggregation; Thrombelastography
PubMed: 1170359
DOI: No ID Found -
Advances in Nephrology From the Necker... 1975
Review
Topics: Adenosine; Antidepressive Agents; Aspirin; Blood Platelets; Complement System Proteins; Endothelium; Glomerulonephritis; Hemostasis; Heparin; Histamine H1 Antagonists; Humans; Immunity; Immunoglobulins; Indomethacin; Kidney Diseases; Meclofenamic Acid; Mopidamol; Phagocytosis; Phenylbutazone; Platelet Aggregation; Prostaglandins; Pyrimidines; Sulfinpyrazone; Tranquilizing Agents; Warfarin
PubMed: 242207
DOI: No ID Found