Correlation of activation and aggregation of platelets. Discrimination between anti-activating and anti-aggregating agents.
Shape change and release reaction indicate different degrees of the complex platelet response termed activation. Aggregation is a variable consequence of activation. Aggregation shows a temperature dependency opposite to that shown by the preceding shape change. Aggregation increases at lower temperature and requires, in contrast to activation, extracellular Ca2+, stirring, and at a low degree of activation the presence of fibrinogen. Aggregation can enhance activation by triggering prostaglandin endoperoxide-thromboxane synthesis. If activation reaches a high level associated with the release reaction, activation is further amplified by prostaglandin endoperoxide-thromboxane synthesis emerging independent of aggregation. These mechanisms of amplification of activation are blocked by indomethacin, an inhibitor of prostaglandin endoperoxide-thromboxane synthesis=anti-activating agent. In contrast, anti-aggregating agents, exemplified here with n-acetyl neuraminic acid, attack the aggregation of activated platelets but neither activation nor prostaglandin endoperoxide-thromboxane synthesis. Its anti-aggregating effect, in addition, enables n-acetyl neuraminic acid to imitate the inhibitory effect of indomethacin on the feedback amplification which results from aggregation. Anti-aggregating agents as characterized here may open a new valuable concept for anti-aggregation in vivo.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011449:Prostaglandin Endoperoxides / Q000096:biosynthesis; D012794:Sialic Acids / Q000494:pharmacology*; D013696:Temperature; D013931:Thromboxanes / Q000096:biosynthesis
D011449:Prostaglandin Endoperoxides; D012794:Sialic Acids; D013931:Thromboxanes; D000244:Adenosine Diphosphate; D004492:Edetic Acid; D002118:Calcium; D007213:Indomethacin