title: Salicylate inhibits thrombopoiesis in rat megakaryocytes by changing the membrane micro-architecture.
abstract: OBJECTIVE
  Salicylate causes drug-induced immune thrombocytopenia. However, some clinical studies indicate the presence of additional mechanisms in the drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. Since salicylate is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis.
  
  
  METHODS
  Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate on the membrane capacitance in rat megakaryocytes. Taking electron microscopic imaging of the cellular surface, we also examined the effects of salicylate on the membrane micro-architecture of megakaryocytes.
  
  
  RESULTS
  Salicylate significantly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging technique. As shown by electron microscopy, salicylate actually halted the process of pro-platelet formation in megakaryocytes.
  
  
  CONCLUSIONS
  This study demonstrated for the first time that salicylate inhibits the process of thrombopoiesis in megakaryocytes, as detected by the decrease in the membrane capacitance. Salicylate-induced changes in the membrane micro-architecture are thought to be responsible for its effects.
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
authors.forename: Asuka
authors.initials: A
authors.lastname: Baba
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Endo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toyama
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ejima
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Matsubara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology*; D034061:Thrombopoiesis / Q000187:drug effects*
chemical_list: D008051:Lipid Bilayers; D012459:Salicylates