期刊
BIOCHEMICAL JOURNAL
卷 473, 期 -, 页码 1-5出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20150934
关键词
calcium; calcium imaging; endoplasmic reticulum; endothelial cell; sigma-1 receptor; store-operated calcium entry
资金
- NIH [DA035926, P30DA013429]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM097335] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P30DA013429, R01DA035926] Funding Source: NIH RePORTER
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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