Valproic acid inhibits ATP-triggered Ca2+release via a p38-dependent mechanism in bEND.3 endothelial cells

Iat Lon Leong, Tien Yao Tsai, Kar Lok Wong, Lian Ru Shiao, Ka Shun Cheng, Paul Chan

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


© 2018 Société Française de Pharmacologie et de Thérapeutique Valproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca2+signaling are hitherto unreported. In this report, we examined the effects of VA on agonist-triggered Ca2+signaling in mouse cortical bEND.3 EC. While VA (100 μm) did not cause an acute inhibition of ATP-triggered Ca2+signaling, a 30-min VA treatment strongly suppressed ATP-triggered intracellular Ca2+release; however, such treatment did not affect Ca2+release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca2+pump, suggesting there was no reduction in Ca2+store size. VA-activated p38 signaling, and VA-induced inhibition of ATP-triggered Ca2+release was prevented by SB203580, a p38 inhibitor, suggesting VA caused the inhibition by activating p38. Remarkably, VA treatment did not affect acetylcholine-triggered Ca2+release, suggesting VA may not inhibit inositol 1,4,5-trisphosphate-induced Ca2+release per se, and may not act directly on Gq or phospholipase C. Taken together, our results suggest VA treatment, via a p38-dependent mechanism, led to an inhibition of purinergic receptor-effector coupling.
Original languageEnglish
Pages (from-to)499-506
Number of pages8
JournalFundamental and Clinical Pharmacology
Issue number5
Publication statusPublished - Oct 1 2018


  • Ca release 2+
  • endothelial cells
  • p38
  • purinergic receptor
  • valproic acid


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