Effects of a polyoxyethylene detergent (Brij 58) on platelet aggregation, release and clotting activity.
Low concentrations of a polyoxyethylene detergent, Brij 58, inhibited the secondary phase of platelet aggregation induced by ADP in human citrated platelet-rich plasma but had no effect on primary aggregation. Thrombin-induced aggregation of washed human platelets suspended in Tyrode's buffer was inhibited after incubation of cells with 4.10(-6) M detergent. Efflux of [14C]serotonin, 45Ca2+ and labile aorta contracting substance (thromboxane A2) and development of prothrombin-converting activity (platelet factor 3) were abolished concomitantly. Aggregation of washed platelets either by sodium arachidonate or by collagen was also inhibited by the same concentration of Brij 58 which inhibited thrombin aggregation. This concentration did not itself produce any release of a cytoplasmic marker, lactate dehydrogenase, from platelets. Higher concentrations of Brij 58, exceeding 4.10(-5) M, lysed the cells liberating lactate dehydrogenase, serotonin and Ca2+. When albumin was included as a platelet stabilizer in the suspending medium the concentration of detergent required for the inhibitory effects was increased ten-fold. This could be attributed to competitive binding of the detergent to albumin, demonstrated with [14C]acetylated Brij 58. A variety of other polyoxyethylene detergents, at concentrations from 8.10(-4) to 5.10(-3) M, also inhibited platelet aggregation induced by thrombin. It is concluded that low concentrations of Brij 58 stabilize the platelets against the action of aggregating agents, while higher concentrations produce membrane destabilization and cell lysis.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010743:Phospholipids / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011092:Polyethylene Glycols; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism
D001095:Arachidonic Acids; D003902:Detergents; D010743:Phospholipids; D012701:Serotonin; D011092:Polyethylene Glycols; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin; D002118:Calcium