Sigma-1 receptor (Sig-1R) is an intracellular chaperone protein with many ligands, located at the endoplasmic reticulum (ER). Binding of cocaine to Sig-1R has previously been found to modulate endothelial functions. In the present study, we show that cocaine dramatically inhibits store-operated Ca2+ entry (SOCE), a Ca2+ influx mechanism promoted by depletion of intracellular Ca2+ stores, in rat brain microvascular endothelial cells (RBMVEC). Using either Sig-1R shRNA or pharmacological inhibition with the unrelated Sig-1R antagonists BD-1063 and NE-100, we show that cocaine-induced SOCE inhibition is dependent on Sig-1R. In addition to revealing new insight into fundamental mechanisms of cocaine-induced changes in endothelial function, these studies indicate an unprecedented role for Sig-1R as a SOCE inhibitor.
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January 2016
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A pseudo-coloured TEM showing a blebbishield from RT4 bladder cancer cells. Courtesy of Goodwin G. Jinesh, Ashish M. Kamat and Kenneth Dunner Jr. (see Jinesh et al. pages 97–105 in this issue). - PDF Icon PDF LinkFront Matter
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December 09 2015
Cocaine inhibits store-operated Ca2+ entry in brain microvascular endothelial cells: critical role for sigma-1 receptors
G. Cristina Brailoiu;
G. Cristina Brailoiu
*Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
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Elena Deliu;
Elena Deliu
†Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
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Linda M. Console-Bram;
Linda M. Console-Bram
†Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
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Jonathan Soboloff;
Jonathan Soboloff
‡Fels Institute for Cancer Research and Molecular Biology and Department of Medical Genetics & Molecular Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
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Mary E. Abood;
Mary E. Abood
†Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
§Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
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Ellen M. Unterwald;
Ellen M. Unterwald
†Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
║Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
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Eugen Brailoiu
Eugen Brailoiu
1
†Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
August 25 2015
Revision Received:
October 13 2015
Accepted:
October 14 2015
Accepted Manuscript online:
October 14 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 Authors; published by Portland Press Limited
2016
Biochem J (2016) 473 (1): 1–5.
Article history
Received:
August 25 2015
Revision Received:
October 13 2015
Accepted:
October 14 2015
Accepted Manuscript online:
October 14 2015
Connected Content
A commentary has been published:
Sigma-1 receptors: a new pathway for the modulation of store-operated calcium entry
Citation
G. Cristina Brailoiu, Elena Deliu, Linda M. Console-Bram, Jonathan Soboloff, Mary E. Abood, Ellen M. Unterwald, Eugen Brailoiu; Cocaine inhibits store-operated Ca2+ entry in brain microvascular endothelial cells: critical role for sigma-1 receptors. Biochem J 1 January 2016; 473 (1): 1–5. doi: https://doi.org/10.1042/BJ20150934
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