Effect of a new antiaggregating chemical on the structure and function of the human platelet.
A new antiaggregating chemical, alpha-(p-(fluoren-9-ylidenemethyl)phenyl)-2-piperidineethanol (RMI 10,393), designated FYPE, was found to be an effective inhibitor of platelet aggregation induced by adenosine diphosphate (ADP), thrombin, collagen, or epinephrine. Effects of the antiaggregant on platelets were concentration dependent. Aggregation was prevented by low concentrations of FYPE that produced in the platelet only minor ultrastructural changes consisting of loss of microtubules and of discoid shape. Low levels of FYPE that prevented platelet aggregation had no effect on platelet ATPase activities but did alter clot retraction, the thrombin-induced shift in electrophoretic mobility and platelet cholinesterase activity. Market decrease in ADP release and increase in adenyl cyclase activity were produced by low levels of FYPE. This study provides a model for evaluation of platelet antiaggregating compounds in vitro.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000097:blood; D000262:Adenylyl Cyclases / Q000097:blood; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects*; D002802:Cholinesterases / Q000097:blood; D003018:Clot Retraction; D003094:Collagen / Q000037:antagonists & inhibitors; D004586:Electrophoresis; D004837:Epinephrine / Q000037:antagonists & inhibitors; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D010880:Piperidines / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors
D010880:Piperidines; D000431:Ethanol; D000244:Adenosine Diphosphate; D003094:Collagen; D002802:Cholinesterases; D013917:Thrombin; D000251:Adenosine Triphosphatases; D000262:Adenylyl Cyclases; D004837:Epinephrine