title: Effect of celecoxib on Ca2+ fluxes and proliferation in MDCK renal tubular cells.
abstract: The effect of celecoxib on renal tubular cells is largely unexplored. In Madin Darby canine kidney (MDCK) cells, the effect of celecoxib on intracellular CaCa2+ concentration ([Ca2+]i) and proliferation was examined by using the Ca(2 +)-sensitive fluorescent dye fura-2 and the viability detecting fluorescent dye tetrazolium, respectively. Celecoxib (> or =1 micro M) caused an increase of [CaCa2+]i in a concentration-dependent manner. Celecoxib-induced [CaCa2+]i increase was partly reduced by removal of extracellular CaCa2+. Celecoxib-induced CaCa2+ influx was independently suggested by MnCa2+ influx-induced fura-2 fluorescence quench. In Ca(2 +)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2 +)-ATPase, caused a monophasic [CaCa2+]i increase, after which celecoxib only induced a tiny [CaCa2+]i increase; conversely, pretreatment with celecoxib completely inhibited thapsigargin-induced [CaCa2+]i increases. U73122, an inhibitor of phospholipase C, abolished ATP (but not celecoxib)-induced [CaCa2+]i increases. Overnight incubation with 1 or 10 micro M celecoxib decreased cell viability by 80% and 100%, respectively. These data indicate that celecoxib evokes a [CaCa2+]i increase in renal tubular cells by stimulating both extracellular CaCa2+ influx and intracellular CaCa2+ release and is highly toxic to renal tubular cells in vitro.
authors.affiliation: Department of Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: J L
authors.initials: JL
authors.lastname: Wang
authors.forename: K L
authors.initials: KL
authors.lastname: Lin
authors.forename: W C
authors.initials: WC
authors.lastname: Chen
authors.forename: C T
authors.initials: CT
authors.lastname: Chou
authors.forename: C J
authors.initials: CJ
authors.lastname: Huang
authors.forename: C S
authors.initials: CS
authors.lastname: Liu
authors.forename: C H
authors.initials: CH
authors.lastname: Hsieh
authors.forename: C H
authors.initials: CH
authors.lastname: Chang
authors.forename: J K
authors.initials: JK
authors.lastname: Huang
authors.forename: H T
authors.initials: HT
authors.lastname: Chang
authors.forename: S I
authors.initials: SI
authors.lastname: Liu
authors.forename: S S
authors.initials: SS
authors.lastname: Hsu
authors.forename: C R
authors.initials: CR
authors.lastname: Jan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000068579:Celecoxib; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D005456:Fluorescent Dyes / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D005456:Fluorescent Dyes; D011720:Pyrazoles; D013449:Sulfonamides; D010738:Type C Phospholipases; D000068579:Celecoxib; D002118:Calcium