Effect of antiggregating drugs on the formation of PGs and cAMP in platelet suspension

• Published in: Blood & Vessel Vol. 9; no. 4; pp. 474 - 478
• Main Authors: TOHJIMA, Toshio, FUNAYAMA, Hideaki, TAKAHASHI, Yoshimi, KUROSAWA, Toshimitsu, SHIOKAWA, Yuichi
• Format: Journal Article
• Language: English
• Published: The Japanese Society on Thrombosis and Hemostasis 1978
• Subjects: antiaggregatingg drugs; cAMP; platetet aggregation; Prostaglandins
• ISSN: 0386-9717; 1884-2372
• DOI: 10.2491/jjsth1970.9.474

Recent studies have indicated that platelet aggregation might be mediated by a decrease in CAMP from basal levels and prostaglandins (PGs) play a major role in mediating platelet aggregation. On the other hand, platelet function is altered in atherosclerosis and thrombosis. In these diseases, platelet adhesion is incleased, platelet's sensitivity to aggregating agents is increased and platelet secresion is enhanced. The administration of antiaggregating drugs is thought to modify and supress one or more of these functions and consequently prevents or delays the formation of thrombi, but in the treatment of these diseases, anticoagulants were not effective sometimes. One of these reasons is that probably mechanism of inhibition of platelet function by antiaggregating agents is varied. In consideration of this point, it is important to clarify the modes of action of antiaggregating drugs in the treatment of these diseases. Drugs such as Heparin, Trasylol, Dextran sulfate, Carbocromen, Prenylamine, Dipyridamole, CDP-choline and α-Tocopherol were incubated with human platelet suspension. The effects of those drugs on platelet aggregation were studied and those on the formation of PGs and cAMP. Material and Methods Human platelets were obtained from platelet rich plasma by centrifugation and were suspended in 134mM NaCl-15mM Tris-HCl buffer pH 7.4. After treatment with drugs, the platelet suspension was separated into two. One was used for platelet aggregation test by aggregometer. The other was further separated into supernatant and platelet fraction by centrifugation, which was used for assays of PGs and cAMP by RIA methods. Results Heparin, Dextran sulfate, and Carbocromen showed the dosedependent inhibitory effect on platelet aggregation induced by thrombin as well as aspirin or PGE1 did. On the other hand, Trasylol, Prenylamine, CDP-choline and Dipyridamole did not show inhibitory effect in vitro at concentrations lower than those of clinical use. Prenylamine and CDP-choline showed inhibitory effect in vitro at concentrations higher than those of clinical use, but α-Tocopherol did not show inhibitory effect in vitro. (Fig. 1) PGs formation showed stepwise decrease both in supernatant and platelet fraction by Heparin and Dextran sulfate. (Fig. 2) PGs formation showed stepwise decrease in platelet fraction by Aspirin and Trasylol, and no change in supernatant fraction. (Fig. 3.) In platelet fraction, PGs formation showed decrease by the high concentration of CDP-choline and stepwise decrease by Carbocromen. In supernatant fraction, Carbocromen showed slight increase of PGs formation at pg order. (Fig. 4.) The high concentration of Prenylamine depressed PGE, PGF2α formation in platelet fraction. On the other hand, it increased cAMP production. (Fig. 5) Group I did not supress the PG formation, and was further separated into subgroups A and B by the ability of cAMP formation. Group II inhibited the PG formation and was further separated into subgroups 1 and 2 by the ability of PG formation in platelet fraction. Conclusion The mechanisms of inhibitory effect in platelets by antiaggregating drugs were varied. It is important to consider the modes of action of each antiaggregating drug in the clinical treatment of thromboembolism.