The effects of lysophosphatidylcholine and related amphiphiles on platelet cytoskeletal assembly.
The effects of lysoPC, four other amphiphiles containing a linear 16 carbon alkane tail and chlorpromazine on platelet cytoskeletal assembly were compared. LysoPC and nonmetabolized amphiphiles all caused time-dependent inhibition followed by potentiation of thrombin-induced aggregation, serotonin secretion and cytoskeletal assembly in gel-filtered platelets, a result which ruled out hydrolysis of the amphiphiles as the mechanism of the time dependence. Hexadecanesulfonate was superior as a potentiator and cetyltrimethyl ammonium bromide (CTAB) was a better inhibitor. On the contrary, inhibition of platelet activation by arachidonate was not effected in a time-dependent manner and the actin-crosslinking proteins, actin-binding protein and myosin, were selectively prevented from incorporation into cytoskeletal cores, although protein phosphorylation and actin polymerization still occurred. Chlorpromazine also showed this selective inhibition of cytoskeletal assembly. LysoPC at concentrations which have been reported to cause development of filopodia did increase slightly the amount of actin present in Triton X-100-insoluble cores but not protein phosphorylation or incorporation of actin-crosslinking proteins. The effective concentrations of lysoPC and chlorpromazine can be predicted from the Meyer-Overton-Mullins rule of anesthesia which indicates their general effectiveness, but their specific effects only partially overlap.
D000199:Actins / Q000378:metabolism; D000476:Alkanesulfonates / Q000494:pharmacology; D017738:Alkanesulfonic Acids; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003599:Cytoskeleton / Q000648:ultrastructure*; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D000199:Actins; D000476:Alkanesulfonates; D017738:Alkanesulfonic Acids; D001095:Arachidonic Acids; D002593:Cetrimonium Compounds; D008244:Lysophosphatidylcholines; D010750:Phosphoproteins; D016718:Arachidonic Acid; D012701:Serotonin; C025737:cetylsulfonic acid; D013917:Thrombin; D002746:Chlorpromazine; D000077286:Cetrimonium