title: Direct coupling between arachidonic acid-induced Ca2+ release and Ca2+ entry in HEK293 cells.
abstract: Arachidonic acid (AA) modulates intracellular Ca2+ signaling via Ca2+ release or/and Ca2+ entry. However, the mechanism underlies either process is unknown; nor is it clear as to whether the two processes are mechanistically linked. By using Fura2/AM, we found that AA induced mobilization of internal Ca2+ store and an increment in Ca2+, Mn2+ and Ba2+ influx in HEK293 cells. The AA-mediated Ca2+ signaling was not due to AA metabolites, and insensitive to capacitative Ca2+ entry inhibitors. Interestingly, isotetrandrine and Gd3+ inhibited both AA-induced Ca2+ release and Ca2+ entry in a concentration-dependent manner without affecting Ca2+ discharge caused by carbachol, caffeine, or thapsigargin. Additionally, similar pattern of inhibition was observed with tetracaine treatment. More importantly, the three compounds exhibited almost equal potent inhibition of AA-initiated Ca2+ release as well as Ca2+ influx. Therefore, this study, for the first time, provides evidence for a direct coupling between AA-mediated Ca2+ release and Ca2+ entry.
authors.affiliation: Institute of Cardiovascular Science at Health Science Center, Peking University, Beijing 100083, PR China. luod@grc.nia.nih.gov
authors.forename: Dali
authors.initials: D
authors.lastname: Luo
authors.forename: Hongli
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Lan
authors.forename: RuiPing
authors.initials: R
authors.lastname: Xiao
authors.forename: Qide
authors.initials: Q
authors.lastname: Han
mesh_terms: D016718:Arachidonic Acid / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002413:Cations, Divalent / Q000378:metabolism; D002460:Cell Line; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D007668:Kidney; D007700:Kinetics; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002413:Cations, Divalent; D016718:Arachidonic Acid; D002110:Caffeine; D019284:Thapsigargin; D002217:Carbachol; D005682:Gadolinium; D002118:Calcium