title: Cocaine inhibits store-operated Ca2+ entry in brain microvascular endothelial cells: critical role for sigma-1 receptors.
abstract: 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 Ca(2+) entry (SOCE), a Ca(2+) influx mechanism promoted by depletion of intracellular Ca(2+) 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.
authors.affiliation: Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
authors.forename: G Cristina
authors.initials: GC
authors.lastname: Brailoiu
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
authors.forename: Elena
authors.initials: E
authors.lastname: Deliu
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Console-Bram
authors.affiliation: 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.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Soboloff
authors.affiliation: 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.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Abood
authors.affiliation: 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.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Unterwald
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A. ebrailou@temple.edu.
authors.forename: Eugen
authors.initials: E
authors.lastname: Brailoiu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017480:Receptors, sigma / Q000819:agonists / Q000502:physiology*; D000097605:Sigma-1 Receptor
chemical_list: D002118:Calcium; D015220:Calcium Channels; D003042:Cocaine; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor
keywords: calcium; calcium imaging; endoplasmic reticulum; endothelial cell; sigma-1 receptor; store-operated calcium entry