title: Effects of valproate on serotonin-induced intracellular calcium mobilization in human platelets.
abstract: OBJECTIVE
  Valproate (VPA) is effectively used in the treatment of bipolar disorder, although the mechanism of action is unclear. In patients with bipolar disorder, 5-hydroxytryptamine (5-HT)-induced intraplatelet calcium (Ca) mobilization has been shown to be enhanced.
  
  
  METHODS
  We examined the effect of VPA on 5-HT-induced Ca response in the platelets of normal subjects, in the presence of a calmodulin antagonist W-7 (N-[6-aminohexyl]-5-chloro-1-naphthalenesulfonamide), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) or PKC inhibitors staurosporine and bisindolylmaleimide II.
  
  
  RESULTS
  VPA inhibited the 5-HT-induced Ca response in a concentration-dependent manner. For calmodulin pathways, W-7 enhanced the 5-HT-stimulated Ca response, which was not affected by VPA. For PKC pathways, PMA reduced the Ca response, although both PKC inhibitors had no effect. PMA, staurosporine or bisindolylmaleimide II reversed the inhibitory effect of VPA on the Ca response, while W-7 did not modify it.
  
  
  CONCLUSIONS
  These findings suggest the possibility that the mechanism of action of VPA may be partly related to PKC signalling.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Akimoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
authors.forename: Katsuji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Takuya
authors.initials: T
authors.lastname: Masui
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010865:Pilot Projects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D018692:Antimanic Agents; D002147:Calmodulin; D012701:Serotonin; D014635:Valproic Acid; D011493:Protein Kinase C; D002118:Calcium