title: Mechanism of bifonazole-induced [Ca2+]i increases in MDCK renal tubular cells.
abstract: The effect of the antifungal drug bifonazole on Ca2+ homeostasis in Madin Darby canine kidney (MDCK) cells was investigated. Cell suspensions were loaded with the Ca2+-sensitive dye fura-2, and the fluorescence changes were measured with a spectrofluorophotometer. At concentrations between 10-80 microM bifonazole increased cytosolic free Ca2+ levels ([Ca2+]i) in a concentration-dependent manner. The Ca2+ signals were partly inhibited by removing extracellular Ca2+. Bifonazole (40 microM) released Ca2+ from the store sensitive to 1 microM thapsigargin, an endopolasmic reticulum Ca2+ pump inhibitor. Bifonazole (40 microM) per se induced capacitative Ca2+ entry while reduced 1 microM thapsigargin-induced capacitative Ca2+ entry. Inositol 1,4,5-trisphosphate may be involved in bifonazole-induced Ca2+ release because inhibiting phospholipase C with 2 microM U73122 partly reduced the bifonazole response. Together, bifonazole increased [Ca2+]i in renal tubular cells by inducing intracellular Ca2+ release and extracellular Ca2+ influx.
authors.affiliation: Department of Medicine, Kaohsiung Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: K J
authors.initials: KJ
authors.lastname: Cho
authors.forename: W
authors.initials: W
authors.lastname: Su
authors.forename: W C
authors.initials: WC
authors.lastname: Chen
authors.forename: Y P
authors.initials: YP
authors.lastname: Law
authors.forename: H C
authors.initials: HC
authors.lastname: Fang
authors.forename: C P
authors.initials: CP
authors.lastname: Liu
authors.forename: J S
authors.initials: JS
authors.lastname: Cheng
authors.forename: K C
authors.initials: KC
authors.lastname: Lee
authors.forename: Y K
authors.initials: YK
authors.lastname: Lo
authors.forename: H T
authors.initials: HT
authors.lastname: Chang
authors.forename: J K
authors.initials: JK
authors.lastname: Huang
authors.forename: C R
authors.initials: CR
authors.lastname: Jan
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism*; D023421:Models, Animal; D019284:Thapsigargin / Q000008:administration & dosage; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; C036596:bifonazole; D002118:Calcium