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

Fundamental & Clinical Pharmacology
Iat-Lon LeongYuk-Man Leung

Abstract

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-dependen...Continue Reading

References

Jul 1, 1979·Archives of Neurology·J Bruni, B J Wilder
Sep 15, 1996·Biological Psychiatry·S R Sczekan, F Strumwasser
Jan 15, 2002·American Journal of Physiology. Cell Physiology·Lisa M SchwiebertErik M Schwiebert
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Terry Kenakin
Feb 24, 2004·Molecular Pharmacology·Martin MichaelisJindrich Cinatl
Apr 10, 2004·Journal of Molecular Endocrinology·B Chini, M Parenti
Jul 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yanlei HaoGuang Chen
Nov 21, 2009·Journal of Affective Disorders·L A SmithC L Bowden
Jul 14, 2010·Neuroscience Letters·Nanchang XieZhaofu Chi
Sep 22, 2010·Journal of Cellular Physiology·Yuk-Man LeungChun-Hsiao Chou
Sep 6, 2011·European Heart Journal·Ulrich Förstermann, William C Sessa
Apr 24, 2012·Neurologia Medico-chirurgica·Satoru OsukaAkira Matsumura
Feb 19, 2013·Progress in Molecular Biology and Translational Science·Peishen ZhaoPeter Chidiac
Aug 24, 2017·Epilepsia·Cecilie Johannessen LandmarkTorbjörn Tomson

❮ Previous
Next ❯

Citations

Jun 18, 2019·Fundamental & Clinical Pharmacology·King-Chuen WuLi-Yun Chang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Forebrain- Circuits

Basal forebrain is a region in the brain important for production of acetylcholine and is the major cholinergic output of the CNS. Discover the latest research on circuits in the basal forebrain here.

Bipolar Disorder

Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.

© 2022 Meta ULC. All rights reserved